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Antibody targeting of phosphatidylserine for detection and immunotherapy of cancer
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Zohar DN , Shoenfeld Y
Yıl :
2018
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Daniela Noa Zohar, Yehuda Shoenfeld Zabludowitz Centre for Autoimmune Diseases, Sheba Medical Centre, Tel-Hashomer, IsraelBelzile et al introduce a novel therapeutic approach for cancer by antibody targeting of phosphatidylserine (PS).1 As is well known, antiphospholipid autoantibodies are associated with hypercoagulability disorders, particularly antiphospholipid syndrome (APS).2 While the hallmark autoantibodies of APS are anti-beta2 glycoprotein and anticardiolipin, over 30 other non-classic autoantibodies were reported in correlation with APS. Particular attention was dedicated to antiphosphatidylserine (aPS) – a remarkable autoantibody that was detected in 68–86% of APS patients.2 aPS is associated with thrombosis, thrombocytopenia and hemolytic anemia.2 Previously, we have described the pathogenicity of aPS on experimental mice models by induction of APS, both through passive transfer of purified human IgG aPS antibodies3 and active immunization, whereas immunized mice with IgG aPS produced high titers of mouse aPS. The results demonstrated a clinical picture of APS by prolonged activated partial thromboplastin time, thrombocytopenia and increased rates of fetal resorptions.4View the review paper by Belzile and colleagues.
Anahtar Kelimeler : antiphospholipids, hypercoagulability, immunotherapy
ISSN: 2253-1556
Cilt: 7
Sayfa: 51 - 53
Sınıflandırma :
Hematoloji %100
2
FDA-approved immunosuppressants targeting staphylococcal superantigens: mechanisms and insights
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Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Krakauer T
Yıl :
2017
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Teresa Krakauer Department of Immunology, Molecular Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA Abstract: Immunostimulating staphylococcal enterotoxin B (SEB) and related superantigenic toxins cause diseases in human beings and laboratory animals by hyperactivating cells of the immune system. These protein toxins bind to the major histocompatibility complex class II (MHC II) molecules and specific Vβ regions of T-cell receptors (TCRs), resulting in the stimulation of both monocytes/macrophages and T lymphocytes. The bridging of TCR with MHC II molecules by superantigens triggers intracellular signaling cascades, resulting in excessive release of proinflammatory mediators and massive polyclonal T-cell proliferation. The early induction of tumor necrosis factor α, interleukin 1 (IL-1), interleukin 2 (IL-2), interferon gamma (IFNγ), and macrophage chemoattractant protein 1 promotes fever, inflammation, and multiple organ injury. The signal transduction pathways for staphylococcal superantigen-induced toxicity downstream from TCR/major histocompatibility complex (MHC) ligation and interaction of cell surface co-stimulatory molecules include the mitogen-activated protein kinase cascades and cytokine receptor signaling, activating nuclear factor kB (NFkB) and the phosphoinositide 3-kinase/mammalian target of rapamycin pathways. Knowledge of host regulation within these activated pathways and molecules initiated by SEB and other superantigens enables the selection of US Food and Drug Administration (FDA)-approved drugs to interrupt and prevent superantigen-induced shock in animal models. This review focuses on the use of FDA-approved immunosuppressants in targeting the signaling pathways induced by staphylococcal superantigens. Keywords: immunosuppressant, superantigen, toxic shock, NFkB, mTORC1
Anahtar Kelimeler : Immunosuppressant, superantigen, toxic shock, mTORC1
ISSN: 2253-1556
Cilt: 6
Sayfa: 17 - 29
Sınıflandırma :
3
Immunotherapy for Medulloblastoma: Current Perspectives
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Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Kabir TF , Kunos CA , Villano JL , Chauhan A
Yıl :
2020
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Tanvir F Kabir,1 Charles A Kunos,2 John L Villano,3 Aman Chauhan3 1Department of Internal Medicine, University of Louisville, Louisville, KY, USA; 2Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA; 3Department of Internal Medicine-Medical Oncology, Markey Cancer Center, University of Kentucky, Lexington, KY, USACorrespondence: Aman Chauhan Email amanchauhan@uky.eduBackground: Immune-mediated therapies have transformed the treatment of metastatic melanoma and renal, bladder, and both small and non-small cell lung carcinomas. However, immunotherapy is yet to demonstrate dramatic results in brain tumors like medulloblastoma for a variety of reasons. Recent pre-clinical and early phase human trials provide encouraging results that may overcome the challenges of central nervous system (CNS) tumors, which include the intrinsic immunosuppressive properties of these cancers, a lack of antigen targets, antigenic variability, and the immune-restrictive site of the CNS. These studies highlight the growing potential of immunotherapy to treat patients with medulloblastoma, a disease that is a frequent cause of morbidity and mortality to children and young adults.Methods: We conducted an inclusive review of the PubMed-indexed literature and studies listed in clinicaltrials.gov using combinations of the keywords medulloblastoma, immunotherapy, CNS tumors, brain tumors, vaccines, oncolytic virus, natural killer, and CAR T to identify trials evaluating immunotherapy in preclinical experiments or in patients with medulloblastoma. Given a limited number of investigations using immunotherapy to treat patients with medulloblastoma, 24 studies were selected for final analysis and manuscript citation.Results: This review presents results from pre-clinical studies in medulloblastoma cell lines, animal models, and the limited trials involving human patients.Conclusion: From our review, we suggest that cancer vaccines, oncolytic viral therapy, natural killer cells, and CAR T therapy hold promise against the innate immunosuppressive properties of medulloblastoma in order to prolong survival. There is an unmet need for immunotherapy regimens that target overexpressed antigens in medulloblastoma tumors. We advocate for more combination treatment clinical trials using conventional surgical and radiochemotherapy approaches in the near-term clinical development.Keywords: medulloblastoma, immunotherapy, vaccines, oncolytic virus, natural killer, CAR T, review
Anahtar Kelimeler : medulloblastoma, immunotherapy, vaccines, oncolytic virus, natural killer, car t, review
ISSN: 2253-1556
Cilt: 9
Sayfa: 57 - 77
Sınıflandırma :
4
Gasdermin D Hypermethylation Inhibits Pyroptosis And LPS-Induced IL-1β Release From NK92 Cells
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Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Muhammad JS , Jayakumar MN , Elemam NM , Venkatachalam T , Raju TK , Hamoudi RA , Maghazachi AA
Yıl :
2019
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Jibran Sualeh Muhammad, Manju Nidagodu Jayakumar, Noha Mousaad Elemam, Thenmozhi Venkatachalam, Tom Kalathil Raju, Rifat Akram Hamoudi, Azzam A Maghazachi College of Medicine, and the Immuno-Oncology Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab EmiratesCorrespondence: Azzam A MaghazachiDepartment of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesEmail amaghazachi@sharjah.ac.aeIntroduction: Although natural killer (NK) are major cells used to treat cancer patients, recent clinical trials showed that NK92 cells can be also used for the same purpose due to their high anti-tumor activity. Here, we examined whether these cells might be inflammatory due to the release of interleukin-1β (IL-1β), and whether the anti-inflammatory molecules dimethyl fumarate (DMF), or monomethyl fumarate (MMF) impair this activity.Methods: NK92 cells were examined for the synthesis and release of IL-1β utilizing RT-PCR and ELISA assay, respectively. The expression of hydroxy-carboxylic acid receptors (HCA)1, HCA2 and HCA3 was detected by immunoblotting, flow cytometry, immunofluorescence and RT-PCR assays. The activation of caspase-1 and Gasdermin D (GSDMD) was evaluated by immunoblot assay. Pyroptosis was demonstrated by immunofluorescence imaging. Expression of DNA methyltransferases (DNMTs) mRNA was determined by whole transcriptome and immunoblot analyses.Results: LPS-induced the release of IL-1β from NK92 cells, whereas DMF or MMF inhibited this induction. The effect of these drugs was due to inhibiting the conversion of procaspase-1 into active caspase-1. NK92 cells highly expressed GSDMD, a pyroptotic-mediated molecule. However, LPS induced the distribution of GSDMD into the cell membranes, corroborated with the presence of pyroptotic bodies, an activity that was inhibited by DMF or MMF. These molecule also inhibited the generation of GSDMD through DNMT-mediated hypermethylation of the promoter region of GSDMD gene. These results were supported by increased expression of DNMTs mRNA as determined by whole transcriptome analysis.Discussion: Our results are the first to show that NK92 cells utilize GSDMD pathway to release IL-1β. Further, DMF and MMF which were previously shown to enhance NK cell cytotoxicity, also inhibit the inflammatory effects of these cells, making them most suitable for treating cancer patients.Keywords: pyroptosis, gasdermin D, NK cells, IL-1β, dimethyl fumarate, monomethyl fumarate
Anahtar Kelimeler : Pyroptosis, Gasdermin D, NK cells, IL-1β, Dimethyl fumarate, Monomethyl fumarate
ISSN: 2253-1556
Cilt: 8
Sayfa: 29 - 41
Sınıflandırma :
5
Toll-like receptors in the pathogenesis of autoimmune diseases: recent and emerging translational developments
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Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Duffy L , Ou2019Reilly SC
Yıl :
2016
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Laura Duffy, Steven C O’Reilly Immunology and Cell Biology Group, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK Abstract: Autoinflammatory diseases are defined as the loss of self-tolerance in which an inflammatory response to self-antigens occurs, which are a significant global burden. Toll-like receptors are key pattern recognition receptors, which integrate signals leading to the activation of transcription factors and ultimately proinflammatory cytokines. Recently, it has become apparent that these are at the nexus of autoinflammatory diseases making them viable and attractive drug targets. The aim of this review was to evaluate the role of innate immunity in autoinflammatory conditions alongside the role of negative regulation while suggesting possible therapeutic targets. Keywords: autoimmunity, toll-like receptors, danger signals, arthritis
Anahtar Kelimeler : autoimmunity, toll-like receptors, danger signals and arthritis
ISSN: 2253-1556
Cilt: 5
Sayfa: 69 - 80
Sınıflandırma :
6
Bacillus Calmette-Guérin (BCG) Therapy for Bladder Cancer: An Update
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Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Guallar-Garrido S , Julián E
Yıl :
2020
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Sandra Guallar-Garrido, Esther Julián Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), SpainCorrespondence: Esther JuliánDepartament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), SpainTel +34 93 5814870Fax +34 93 5812387Email esther.julian@uab.catAbstract: Physicians treating patients affected by nonmuscle-invasive bladder cancer (NMIBC) have been in shock during the last six years since manufacturing restrictions on the production of the first-option medicine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), have resulted in worldwide shortages. This shortage of BCG has led to a rethinking of the established treatment guidelines for the rationing of the administration of BCG. Some possible schedule modifications consist of a decrease in the length of maintenance treatment, a reduction in the dose of BCG in intravesical instillations or the use of different BCG substrains. All these strategies have been considered valuable in times of BCG shortage. In addition, the lack of availability of BCG has also led to the general recognition of the need to find new treatment options for these patients so that they are not dependent on a single treatment. Few alternatives are committed to definitively replacing BCG intravesical instillations, but several options are being evaluated to improve its efficacy or to combine it with other chemotherapeutic or immunotherapeutic options that can also improve its effect. In this article, we review the current state of the treatment with BCG in terms of all of the aforementioned aspects.Keywords: mycobacteria, nonmuscle invasive, immunotherapy, alternative treatment
Anahtar Kelimeler : mycobacteria, nonmuscle invasive, immunotherapy, alternative treatment
ISSN: 2253-1556
Cilt: 9
Sayfa: 1 - 11
Sınıflandırma :
7
Assessing Immune Response to SARS-CoV-2 Infection
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Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Shurin MR , Morris A , Wells A , Wheeler SE
Yıl :
2020
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Michael R Shurin,1,2 Alison Morris,3 Alan Wells,1 Sarah E Wheeler1 1Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 3Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USACorrespondence: Michael R Shurin Email shurinmr@upmc.eduIn the XXI century, we have already witnessed the global spread of three previously unknown coronaviruses. In 2002, the first known case of severe acute respiratory syndrome (SARS) occurred in China and SARS coronavirus (SARS-CoV) was identified in 2003.1 Before SARS pandemic was declared to be over in summer of 2003, about 8500 cases were reported, including almost 900 deaths in 32 countries. Ten years later, in 2012, a novel coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), was isolated and was proven to be associated with several clusters of cases, first in the Arabian Peninsula and then in other countries. As a result, almost 2500 cases including more than 850 deaths in 27 countries have been reported.2 In 2019, a novel β-coronavirus caused severe and even fatal pneumonia in Wuhan China, and rapidly spread to other provinces of China and other countries in 2020. The World Health Organization (WHO) on March 11, 2020, declared coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a pandemic. By mid-May 2020, more than 300,000 people have died and over 4,000,000 have been infected by the coronavirus in almost 200 countries and territories worldwide.
Anahtar Kelimeler : sars-cov-2, covid-19, serology, coronavirus, immunodiagnostics
ISSN: 2253-1556
Cilt: 9
Sayfa: 111 - 114
Sınıflandırma :
8
Immunoinformatics and Vaccine Development: An Overview
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Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Oli AN , Obialor WO , Ifeanyichukwu MO , Odimegwu DC , Okoyeh JN , Emechebe GO , Adejumo SA , Ibeanu GC
Yıl :
2020
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Angus Nnamdi Oli,1 Wilson Okechukwu Obialor,1 Martins Ositadimma Ifeanyichukwu,2,3 Damian Chukwu Odimegwu,4 Jude Nnaemeka Okoyeh,5 George Ogonna Emechebe,6 Samson Adedeji Adejumo,1 Gordon C Ibeanu7 1Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Nigeria; 2Department of Immunology, College of Health Sciences, Faculty of Medicine, Nnamdi Azikiwe University, Anambra, Nigeria; 3Department of Medical Laboratory Science,Faculty of Health Science and Technology, College of Health Sciences, Nnamdi Azikiwe University,Nnewi Campus, Nnewi, Nigeria; 4Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka, Enugu, Nigeria; 5Department of Biology and Clinical Laboratory Science, Division of Arts and Sciences, Neumann University, Aston, PA 19014-1298, USA; 6Department of Pediatrics, Faculty of Clinical Medicine, Chukwuemeka Odumegwu Ojukwu University, Awka, Nigeria; 7Department of Pharmaceutical Science, North Carolina Central University, Durham, NC 27707, USACorrespondence: Angus Nnamdi Oli Email an.oli@unizik.edu.ngAbstract: The use of vaccines have resulted in a remarkable improvement in global health. It has saved several lives, reduced treatment costs and raised the quality of animal and human lives. Current traditional vaccines came empirically with either vague or completely no knowledge of how they modulate our immune system. Even at the face of potential vaccine design advance, immune-related concerns (as seen with specific vulnerable populations, cases of emerging/re-emerging infectious disease, pathogens with complex lifecycle and antigenic variability, need for personalized vaccinations, and concerns for vaccines’ immunological safety -specifically vaccine likelihood to trigger non-antigen-specific responses that may cause autoimmunity and vaccine allergy) are being raised. And these concerns have driven immunologists toward research for a better approach to vaccine design that will consider these challenges. Currently, immunoinformatics has paved the way for a better understanding of some infectious disease pathogenesis, diagnosis, immune system response and computational vaccinology. The importance of this immunoinformatics in the study of infectious diseases is diverse in terms of computational approaches used, but is united by common qualities related to host–pathogen relationship. Bioinformatics methods are also used to assign functions to uncharacterized genes which can be targeted as a candidate in vaccine design and can be a better approach toward the inclusion of women that are pregnant into vaccine trials and programs. The essence of this review is to give insight into the need to focus on novel computational, experimental and computation-driven experimental approaches for studying of host–pathogen interactions and thus making a case for its use in vaccine development.Keywords: immunoinformatics, computational vaccinology, vaccine design, emerging infections, immune system; vaccinology
Anahtar Kelimeler : immunoinformatics, computational vaccinology, vaccine design, emerging infections, immune system)
ISSN: 2253-1556
Cilt: 9
Sayfa: 13 - 30
Sınıflandırma :
9
Factors Associated With Adherence To Immunosuppressive Therapy And Barriers In Asian Kidney Transplant Recipients
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Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Ganjali R , Ghorban Sabbagh M , Nazemiyan F , Mamdouhi F , Badiee Aval S , Taherzadeh Z , Heshmati Nabavi F , Golmakani R , Tohidinezhad F , Eslami S
Yıl :
2019
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Raheleh Ganjali,1 Mahin Ghorban Sabbagh,2,3 Fatemeh Nazemiyan,2,4 Fereshteh Mamdouhi,2,3 Shapour Badiee Aval,5 Zhila Taherzadeh,6 Fatemeh Heshmati Nabavi,7 Reza Golmakani,8 Fariba Tohidinezhad,1 Saeid Eslami1,9,10 1Department of Medical Informatics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 2Kidney Transplantation Complications Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 3Department of Nephrology, Montaseriyeh Organ Transplantation Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; 4Department of Nephrology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; 5Complementary Medicine Research Center, Faculty of Traditional Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 6Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 7School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran; 8Department of Emergency Medicine, Doctor Shariati Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; 9Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 10Department of Medical Informatics, University of Amsterdam, Amsterdam, The NetherlandsCorrespondence: Saeid EslamiDepartment of Medical Informatics, Mashhad University of Medical Sciences, Azadi Street, Mashhad, IranTel +98 513 800 2429Fax +98 513 800 2445Email Eslamis@mums.ac.irBackground: Medication non-adherence is the major risk factor for rejection episodes. The aim of this study was to determine the risk factors associated with adherence to immunosuppressive regimen and its barriers among kidney transplant (KT) recipients.Methods: A cross-sectional study was performed in two outpatient post-transplant clinics in Mashhad, northeast of Iran. All patients who attended the clinics from August to October 2017 were included. Patients’s knowledge, adherence to immunosuppressive regimen, and quality of life were measured using the Kidney Transplant Understanding Tool, Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS), and SF-12V2 questionnaire, respectively. The barriers in adhering immunosuppressive regimen were investigated by Immunosuppressive Therapy Barriers Scale. Logistic regression was used to screen the significant risk factors of medication non-adherence.Results: In this study, 244 KT recipients were included with a mean age of 39.6±12.5 years. Based on the BAASIS score, 111 (45.5%) patients were adherent to immunosuppressive regimen. Female patients were more likely to be adherent (OR=0.48, p<0.01). The patients with higher level of quality of life were more likely to follow immunosuppressive medications (OR=1.078, p<0.05). The main barriers were as follows: concurrent use of many immunosuppressants, lack of knowledge about the usefulness of immunosuppressive medications, confusion in medication taking, and difficulty in remembering medication taking.Conclusion: More than half of the KT recipients were non-adherence to immunosuppressive regimen. These findings highlight the need for designing interventions in order to reduce or eliminate these barriers and consequently increase medication adherence among KT recipients.Keywords: immunosuppressive regimen, medication adherence, quality of life, kidney transplantation
Anahtar Kelimeler : immunosuppressive regimen- medication adherence- quality of life- kidney transplantation.
ISSN: 2253-1556
Cilt: 8
Sayfa: 53 - 62
Sınıflandırma :
10
Alteration of gene expression profile in CD3+ T-cells after downregulating MALT1
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Wang X , Lu S , Xiao Y , Xu L , Zhou L , Hu JY , Li B , Zeng C , Li Y
Yıl :
2018
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Xu Wang,1,2,* Shuai Lu,1,2,* Yankai Xiao,1,2 Ling Xu,2,3 Lingling Zhou,1,2 Junyan Hu,2 Bo Li,1,2 Chengwu Zeng,1,2 Yangqiu Li1–3 1Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Institute of Hematology, Jinan University, Guangzhou, 510632, People’s Republic of China; 3Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China *These authors contributed equally to this work Background: T cell immunodeficiency is a common feature in patients with different kinds of hematological disease such as T cell non-Hodgkin lymphoma (T-NHL), B cells NHL (B-NHL), NK/T cell NHL (NK/T-CL) and acute myeloid leukemia (AML). In our recent research, we found that significantly lower expression levels in MALT1 and NF-κB were related to suppression of T cell activation. Therefore, this study was conducted to further investigate the role of downregulating MALT1 in the development of immunodeficiency in T cells.Methods: We induced activation inhibition in CD3+ T cells by MALT1 knockdown. Then we characterized the gene expression profile after MALT1 suppression by microarray analysis.Result: The differentially expressed genes were ZAP-70, p65, MDM2, ATM, NFATC2 which participate in the NF-κB, p53, and NFAT pathways in CD3+ T cells after MALT1 downregulation.Conclusion: MALT1 suppression may contribute to immunodeficiency in T cells via suppression of T cell activation and proliferation pathways. These data may help to explain some of the characteristics of immunodeficiency of T cells. Keywords: CD3+ T-cells, MALT1, immunodeficiency, T-cell activation, microarray
Anahtar Kelimeler : CD3+ T cells, MALT1, Immunodeficiency, T cell activation, Microarray
ISSN: 2253-1556
Cilt: 7
Sayfa: 77 - 81
Sınıflandırma :
Biyotıp %100
Hematoloji %91
11
Therapeutic vaccines in non-small cell lung cancer
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Socola F , Scherfenberg N , Raez LE
Yıl :
2013
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Francisco Socola,1 Naomi Scherfenberg,2 Luis E Raez3 1Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami Leonard M Miller School of Medicine, Miami, Florida, USA; 2University of Miami Leonard M Miller School of Medicine, Miami, Florida, USA; 3Thoracic Oncology Program, Memorial Cancer Institute, Memorial Health Care System, Pembroke Pines, Florida, USA Abstract: Non-small cell lung cancer (NSCLC) unfortunately carries a very poor prognosis. Patients usually do not become symptomatic, and therefore do not seek treatment, until the cancer is advanced and it is too late to employ curative treatment options. New therapeutic options are urgently needed for NSCLC, because even current targeted therapies cure very few patients. Active immunotherapy is an option that is gaining more attention. A delicate and complex interplay exists between the tumor and the immune system. Solid tumors utilize a variety of mechanisms to evade immune detection. However, if the immune system can be stimulated to recognize the tumor as foreign, tumor cells can be specifically eliminated with little systemic toxicity. A number of vaccines designed to boost immunity against NSCLC are currently undergoing investigation in phase III clinical trials. Belagenpumatucel-L, an allogeneic cell vaccine that decreases transforming growth factor (TGF-β) in the tumor microenvironment, releases the immune suppression caused by the tumor and it has shown efficacy in a wide array of patients with advanced NSCLC. Melanoma-associated antigen A3 (MAGE-A3), an antigen-based vaccine, has shown promising results in MAGE-A3+ NSCLC patients who have undergone complete surgical resection. L-BLP25 and TG4010 are both antigenic vaccines that target the Mucin 1 protein (MUC-1), a proto-oncogene that is commonly mutated in solid tumors. CIMAVax is a recombinant human epidermal growth factor (EGF) vaccine that induces anti-EGF antibody production and prevents EGF from binding to its receptor. These vaccines may significantly improve survival and quality of life for patients with an otherwise dismal NSCLC prognosis. This review is intended to give an overview of the current data and the most promising studies of active immunotherapy for NSCLC. Keywords: immunotherapy, non-small cell lung cancer, Belagenpumatucel-L, melanoma-associated antigen A3 (MAGE-A3), L-BLP25, TG4010, CIMAVax
Anahtar Kelimeler : Immunotherapy, non-small cell lung cancer. Belagenpumatucel-L, melanoma-associated antigen A3 (MAGE-A3), L-BLP25, TG4010 and CIMAVax.
ISSN: 2253-1556
Cilt: 2013
Sayı: 1
Sayfa: 115 - 124
Sınıflandırma :
12
Immunotherapy for the treatment of Alzheimer's disease: amyloid-β or tau, which is the right target?
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Castillo-Carranza DL , Guerrero-Muñoz MJ , Kayed R
Yıl :
2013
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Diana L Castillo-Carranza,1,2 Marcos J Guerrero-Muñoz,1,2 Rakez Kayed1–31Mitchell Center for Neurodegenerative Diseases, 2Departments of Neurology, Neuroscience, and Cell Biology, 3Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USAAbstract: Alzheimer's disease (AD) is characterized by the presence of amyloid plaques composed mainly of amyloid-β (Aβ) protein. Overproduction or slow clearance of Aβ initiates a cascade of pathologic events that may lead to formation of neurofibrillary tangles, neuronal cell death, and dementia. Although immunotherapy in animal models has been demonstrated to be successful at removing plaques or prefibrillar forms of Aβ, clinical trials have yielded disappointing results. The lack of substantial cognitive improvement obtained by targeting Aβ raises the question of whether or not this is the correct target. Another important pathologic process in the AD brain is tau aggregation, which seems to become independent once initiated. Recent studies targeting tau in AD mouse models have displayed evidence of cognitive improvement, providing a novel therapeutic approach for the treatment of AD. In this review, we describe new advances in immunotherapy targeting Aβ peptide and tau protein, as well as future directions.Keywords: immunotherapy, Alzheimer's disease, β-amyloid, tau
Anahtar Kelimeler : Immunotherapy, Alzheimeru2019s disease, β-amyloid
ISSN: 2253-1556
Cilt: 2014
Sayı: 1
Sayfa: 19 - 28
Sınıflandırma :
13
Place in therapy of rituximab in the treatment of granulomatosis with polyangiitis and microscopic polyangiitis
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Shah S , Geetha D
Yıl :
2015
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Shivani Shah, Duvuru Geetha Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Granulomatosis with polyangiitis and microscopic polyangiitis are small vessel vasculitides characterized by circulating antineutrophil circulating antibodies. Standard treatment for active severe disease has consisted of cyclophosphamide with glucocorticoids with or without plasmapheresis, which achieves approximately 75% sustained remission, but carries significant adverse effects such as malignancy, infertility, leukopenia, and infections. The role of B cells in the pathogenesis of anti-neutrophil circulating antibodies-associated vasculitis has been established, and as such, rituximab, a monoclonal anti-CD20 antibody, has been studied in treatment of active granulomatosis with polyangiitis and microscopic polyangiitis (induction) and in maintaining remission. Rituximab has been shown to be effective in inducing remission in several retrospective studies in patients with refractory disease or cyclophosphamide intolerance. The RAVE and RITUXVAS trials demonstrated rituximab is a noninferior alternative to standard cyclophosphamide-based therapy; however, its role in elderly patients and patients with severe renal disease warrants further investigation. Rituximab has been compared with azathioprine for maintaining remission in the MAINRITSAN trial and may be more efficacious in maintaining remission in patients treated with cyclophosphamide induction. Rituximab is not without risks and carries a similar adverse event risk rate as cyclophosphamide in randomized control trials. However, its use can be considered over cyclophosphamide in patients who have relapsing or refractory disease or in young patients seeking to preserve fertility. Keywords: rituximab, ANCA-associated vasculitis, GPA, MPA, induction therapy, maintenance therapy
Anahtar Kelimeler : Rituximab, ANCA vasculitis, induction therapy, maintenance therapy
ISSN: 2253-1556
Cilt: 2015
Sayı: 1
Sayfa: 173 - 183
Sınıflandırma :
14
Melanoma treatment in review
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Domingues B , Lopes JM , Soares P , Pópulo H
Yıl :
2018
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Beatriz Domingues,1–3 José Manuel Lopes,1,2,4,5 Paula Soares,1,2,5 Helena Pópulo1,2 1Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal; 2Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; 3Faculty of Sciences, University of Porto, Porto, Portugal; 4Department of Pathology, Hospital S João, Porto, Portugal; 5Department of Pathology, Medical Faculty, University of Porto, Porto, Portugal Abstract: Melanoma represents the most aggressive and the deadliest form of skin cancer. Current therapeutic approaches include surgical resection, chemotherapy, photodynamic therapy, immunotherapy, biochemotherapy, and targeted therapy. The therapeutic strategy can include single agents or combined therapies, depending on the patient’s health, stage, and location of the tumor. The efficiency of these treatments can be decreased due to the development of diverse resistance mechanisms. New therapeutic targets have emerged from studies of the genetic profile of melanocytes and from the identification of molecular factors involved in the pathogenesis of the malignant transformation. In this review, we aim to survey therapies approved and under evaluation for melanoma treatment and relevant research on the molecular mechanisms underlying melanomagenesis. Keywords: cancer, melanoma, therapy, targets
Anahtar Kelimeler : cancer, melanoma, therapy, targets
ISSN: 2253-1556
Cilt: 7
Sayfa: 35 - 49
Sınıflandırma :
15
Role of Chemokines and Chemokine Receptors in Rheumatoid Arthritis
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Elemam NM , Hannawi S , Maghazachi AA
Yıl :
2020
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Noha Mousaad Elemam,1 Suad Hannawi,2 Azzam A Maghazachi1 1College of Medicine and Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates; 2Ministry of Health and Prevention, Department of Rheumatology, Dubai, United Arab EmiratesCorrespondence: Azzam A MaghazachiCollege of Medicine and Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesEmail amagazachi@sharjah.ac.aeAbstract: Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases and a prototypic inflammatory disease, affecting the small joints of the hands and feet. Chemokines and chemokine receptors play a critical role in RA pathogenesis via immune cells recruitment. Several chemokines and chemokine receptors are abundant in the peripheral blood and in the local inflamed joints of RA. Furthermore, synthetic and biologics disease modifying anti rheumatic drugs have been reported to affect chemokines expression. Thus, many studies have focused on targeting chemokines and chemokine receptors, where some have shown positive promising results. However, most of the chemokine blockers in human trials of RA treatment displayed some failures that can be attributed to several reasons in their structures and binding affinities. Nevertheless, targeting chemokines will continue to be under development, in order to improve their therapeutic potentials in RA and other autoimmune diseases. In this review we provide an up-to-date knowledge regarding the role of chemokines and chemokine receptors in RA with an emphasis on their activities on immune cells. We also discussed the effects of drugs targeting those molecules in RA. This knowledge might provide impetus for developing new therapeutic modalities to treat this chronic disease.Keywords: rheumatoid arthritis, chemokines, immunotherapy, immunotargets, chemokine receptors, drugs
Anahtar Kelimeler : rheumatoid arthritis, chemokines, immunotherapy, immunotargets, chemokine receptors, drugs
ISSN: 2253-1556
Cilt: 9
Sayfa: 43 - 56
Sınıflandırma :
16
Emerging role of Natural killer cells in oncolytic virotherapy
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Bhat R , Rommelaere J
Yıl :
2015
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Rauf Bhat, Jean Rommelaere Division of Tumor Virology, German Cancer Research Center, Heidelberg, Germany Abstract: Natural killer (NK) cells constitute a subtype of lymphocytes that initiate innate immune responses against tumors and virus-infected cells. The ability of NK cells to kill target cells or to produce cytokines depends on the balance between signals from activating and inhibitory cell-surface receptors. Therapies with NK cells involve activation of endogenous NK cells and/or exogenous transfer by hematopoietic stem cell transplantation/adoptive cell therapy. To exploit the diverse functional abilities of NK cells for cancer immunotherapy, it is important to understand NK cell biology and the underlying regulatory mechanisms. The state of immune suppression prevalent in malignancies creates the need for innovative therapies. Oncolytic viruses are novel anticancer agents showing selective tropism for tumor cells and lacking pathogenicity in humans, but the use of oncolytic virotherapy (OVT) presents multiple challenges. An increasing body of evidence suggests that the host immune response may critically influence the outcome of OVT. Classically, the immune system is thought to limit the efficacy of therapy through virus clearance mediated by innate immune effectors or through adaptive antiviral immune responses eliminating infected cells. Effective strategies do need to be designed in OVT to circumvent the early antiviral activity of NK cells and to augment late NK-cell-mediated antitumor responses. The intrinsic immunostimulating capacity of oncolytic viruses and the possibility of engineering them to express heterologous immunostimulatory molecules (eg, cytokines) support the use of these agents to enhance antitumor immune responses besides inducing direct oncolytic effects. OVT has indeed shown promising therapeutic outcomes in various clinical trials. Here, we review the biology of NK cells, strategies involving NK cells for achieving cancer therapy, and, more particularly, the emerging role of NK cells in OVT. Keywords: natural killer cells, parvovirus, oncolytic virus, tumors, virotherapy
Anahtar Kelimeler : Natural killer cells, Parvovirus, Oncolytic virus, Tumors, VirotherapynAbbreviations: NK cells, natural killer cells, oncolytic viruses, oncolytic virotherapy, killer inhibitory receptors, tumor associated antigens, u201Cou201D in front of a virus acronym (e.g. oHSV) stands for u201Concolyticu201D.
ISSN: 2253-1556
Cilt: 2015
Sayı: 1
Sayfa: 65 - 77
Sınıflandırma :
Biyotıp %100
Viroloji %76
17
Novel Resolution Mediators of Severe Systemic Inflammation
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Gudernatsch V , Stefańczyk SA , Mirakaj V
Yıl :
2020
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Verena Gudernatsch, Sylwia Anna Stefańczyk, Valbona Mirakaj Molecular Intensive Care Medicine, Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, GermanyCorrespondence: Valbona MirakajMolecular Intensive Care Medicine, Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Eberhard Karls University Tübingen, Hoppe-Seyler-Straße 3, Tübingen 72076, GermanyTel +49 7071 29-86622Fax +49 7071 29-5533Email valbona.mirakaj@uni-tuebingen.deAbstract: Nonresolving inflammation, a hallmark of underlying severe inflammatory processes such as sepsis, acute respiratory distress syndrome and multiple organ failure is a major cause of admission to the intensive care unit and high mortality rates. Many survivors develop new functional limitations and health problems, and in cases of sepsis, approximately 40% of patients are rehospitalized within three months. Over the last few decades, better treatment approaches have been adopted. Nevertheless, the lack of knowledge underlying the complex pathophysiology of the inflammatory response organized by numerous mediators and the induction of complex networks impede curative therapy. Thus, increasing evidence indicates that resolution of an acute inflammatory response, considered an active process, is the ideal outcome that leads to tissue restoration and organ function. Many mediators have been identified as immunoresolvents, but only a few have been shown to contribute to both the initial and resolution phases of severe systemic inflammation, and these agents might finally substantially impact the therapeutic approach to severe inflammatory processes. In this review, we depict different resolution mediators/immunoresolvents contributing to resolution programmes specifically related to life-threatening severe inflammatory processes.Keywords: inflammation, resolution, specialized lipid mediators, neuronal guidance protein, sepsis, immunoresolvents
Anahtar Kelimeler : inflammation, resolution, specialized lipid mediators, neuronal guidance protein, sepsis, immunoresolvents
ISSN: 2253-1556
Cilt: 9
Sayfa: 31 - 41
Sınıflandırma :
18
Harnessing immunosurveillance: current developments and future directions in cancer immunotherapy
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Drakes ML , Stiff PJ
Yıl :
2014
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Maureen L Drakes, Patrick J Stiff Department of Medicine, Division of Hematology and Oncology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA Abstract: Despite improved methods of cancer detection and disease management over the last few decades, cancer remains a major public health problem in many societies. Conventional therapies, such as chemotherapy, radiation, and surgery, are not usually sufficient to prevent disease recurrence. Therefore, efforts have been focused on developing novel therapies to manage metastatic disease and to prolong disease-free and overall survival, by modulating the immune system to alleviate immunosuppression, and to enhance antitumor immunity. This review discusses protumor mechanisms in patients that circumvent host immunosurveillance, and addresses current immunotherapy modalities designed to target these mechanisms. Given the complexity of cancer immunosuppressive mechanisms, we propose that identification of novel disease biomarkers will drive the development of more targeted immunotherapy. Finally, administration of different classes of immunotherapy in combination regimens, will be the ultimate route to impact low survival rates in advanced cancer patients. Keywords: cancer, immunotherapy, immunosurveillance, immunosuppression, dendritic cells, T-cells
Anahtar Kelimeler : cancer, immunotherapy, immunosurveillance, immune suppression, dendritic cells, T cells
ISSN: 2253-1556
Cilt: 2014
Sayı: 1
Sayfa: 151 - 165
Sınıflandırma :
19
T cell immunoglobulin domain and mucin domain-3 as an emerging target for immunotherapy in cancer management
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Yoneda A , Jinushi M
Yıl :
2013
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Akihiro Yoneda, Masahisa Jinushi Research Center for Infection-associated Cancer, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan Abstract: Cancer-induced immunosuppression significantly impacts tumors, rendering them the ability to acquire aggressive and treatment-resistant phenotypes. The recent clinical success of drugs targeting the immunosuppressive machinery of tumors highlights the importance of identifying novel drugs that effectively augment antitumor immunity and elicit clinical remission in advanced tumors. T cell immunoglobulin domain and mucin domain-3 (TIM-3) is a critical immunoregulatory molecule that links pattern recognition-mediated innate sensing with antigen-specific immune responses. Recent evidence has elucidated the potential utility of drugs targeting TIM-3 in inducing antitumor responses, particularly in synergy with conventional anticancer regimens. Herein, we provide a comprehensive overview, as well as future perspectives, regarding the role of TIM-3 as an emerging target that may improve clinical responses for cancer patients. Keywords: tumor immunoevasion, antibody, immunosuppression, antitumor response, TIM-3
Anahtar Kelimeler : TIM-3, tumor immunoevasion, cancer immunotherapy, antibody
ISSN: 2253-1556
Cilt: 2013
Sayı: 1
Sayfa: 135 - 141
Sınıflandırma :
Biyotıp %100
Apoptoz %32
Antikorlar %28
20
Oncogenes in immune cells as potential therapeutic targets
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Zakiryanova GK , Wheeler S , Shurin MR
Yıl :
2018
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Gulnur K Zakiryanova,1 Sarah Wheeler,2 Michael R Shurin2 1Department Biophysics and Biomedicine, Faculty Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty, Kazakhstan; 2Division of Clinical Immunopathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Abstract: The role of deregulated expression of oncogenes and tumor-suppressor genes in tumor development has been intensively investigated for decades. However, expression of oncogenes and their potential role in immune cell defects during carcinogenesis and tumor progression have not been thoroughly assessed. The defects in proto-oncogenes have been well documented and evaluated mostly in tumor cells, despite the fact that proto-oncogenes are expressed in all cells, including cells of the immune system. In this review, key studies from immune-mediated diseases that may be associated with oncogene signaling pathways are refocused to provide groundwork for beginning to understand the effects of oncogenes in and on the cancer-related immune system dysfunction. Keywords: oncogenes, immune cells, NK cells, Myc, cancer
Anahtar Kelimeler : oncogenes, immune cells, NK cells, cancer
ISSN: 2253-1556
Cilt: 7
Sayfa: 21 - 28
Sınıflandırma :
21
Targeting innate immunity to downmodulate adaptive immunity and reverse type 1 diabetes
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Itoh A , Ridgway WM
Yıl :
2017
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Arata Itoh, William M Ridgway Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, OH, USA Abstract: Type 1 diabetes (T1D) is characterized by specific destruction of pancreatic insulin-producing beta cells accompanied by evidence of beta-cell-directed autoimmunity such as autoreactive T cells and islet autoantibodies (IAAs). Currently, T1D cannot be prevented or reversed in humans. T1D is easy to prevent in the nonobese diabetic (NOD) spontaneous mouse model but reversing new-onset T1D in mice is more difficult. Since the discovery of the T-cell receptor in the 1980s and the subsequent identification of autoreactive T cells directed toward beta-cell antigens (eg, insulin, glutamic acid decarboxylase), the dream of antigen-specific immunotherapy has dominated the field with its promise of specificity and limited side effects. While such approaches have worked in the NOD mouse, however, dozens of human trials have failed. Broader immunosuppressive approaches (originally cyclosporine, subsequently anti-CD3 antibody) have shown partial successes (e.g., prolonged C peptide preservation) but no major therapeutic efficacy or disease reversal. Human prevention trials have failed, despite the ease of such approaches in the NOD mouse. In the past 50 years, the incidence of T1D has increased dramatically, and one explanation is the “hygiene hypothesis”, which suggests that decreased exposure of the innate immune system to environmental immune stimulants (e.g., bacterial products such as Toll-like receptor (TLR) 4-stimulating lipopolysaccharide [LPS]) dramatically affects the adaptive immune system and increases subsequent autoimmunity. We have tested the role of innate immunity in autoimmune T1D by treating acute-onset T1D in NOD mice with anti-TLR4/MD-2 agonistic antibodies and have shown a high rate of disease reversal. The TLR4 antibodies do not directly stimulate T cells but induce tolerogenic antigen-presenting cells (APCs) that mediate decreased adaptive T-cell responses. Here, we review our current knowledge and suggest future prospects for targeting innate immunity in T1D immunotherapy. Keywords: type 1 diabetes, antigen-specific therapy, innate immunity, Toll-like receptors
Anahtar Kelimeler : Type 1 diabetes, Antigen-specific therapy, Innate immunity, Toll-like receptors
ISSN: 2253-1556
Cilt: 6
Sayfa: 31 - 38
Sınıflandırma :
22
Immunotherapy in the management of melanoma: current status
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Alston D , Brewer JD
Yıl :
2013
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Dylan Alston,1 Jerry D Brewer21Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, 2Mayo Clinic, Rochester, MN, USAAbstract: As the rate of melanoma continues to increase, so does the need for more effective and durable therapies. Despite considerable research, the management of advanced disease remains challenging. Numerous therapies are being investigated, many of which aim at upregulating the immune system's innate ability to attack the tumor. Cytotoxic T lymphocyte antigen 4 antibodies are immune stimulants that act as negative regulators of the immune system by modifying an antitumor T-cell response. Ipilimumab, one such cytotoxic T lymphocyte antigen 4 antibody, and vemurafenib, a BRAF competitive inhibitor, were approved as first-line therapies in 2011 due to improved survival rates versus standard chemotherapy. Allovectin-7 is a lipid plasmid that encodes for major histone compatibility complex DNA sequences. It has led to increases in cytotoxic T-cell production, which subsequently attacks the tumor. OncoVEX, an oncolytic herpes virus, and PV-10, a chemoablative agent, have yielded promising results in metastatic lesions and have demonstrated a unique "bystandarder" phenomenon. In this paper we review the basics of melanoma from the pathophysiology, risk factors, signs, diagnostic approaches, and current status of immunologic management of melanoma.Keywords: melanoma, immunotherapy, ipilimumab, vemurafenib, OncoVEX, Allovectin-7
Anahtar Kelimeler : melanoma, immunotherapy, ipilimumab, vemurafenib, OncoVEX, Allovectin-7
ISSN: 2253-1556
Cilt: 2013
Sayı: 1
Sayfa: 1 - 10
Sınıflandırma :
23
Antigen-based immunotherapy for the treatment of acute lymphoblastic leukemia: the emerging role of blinatumomab
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Litzow MR
Yıl :
2014
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Mark R LitzowMayo Clinic, Rochester, MN, USAAbstract: Acute lymphoblastic leukemia (ALL) arises from immature B and T lymphoblasts. An increasing array of cytogenetic and molecular markers have been identified in ALL, which allows for increasingly sophisticated prognostication, as well as identification of potential new targets for therapy. The treatment of ALL in children has shown astounding success in the last 50 years, with more than 90% of children now able to be cured of their ALL. In adults, these success rates have not been duplicated. However, the use of pediatric-intensive regimens in young adults has shown increasing success. The use of monoclonal antibodies conjugated to drugs, immunotoxins, and cells also has shown early success and promises to enhance the outcome of newly diagnosed patients. Blinatumomab, a bispecific T-cell engager antibody, brings a malignant B cell in proximity to a T cell with redirected lysis. This antibody construct has shown promising results in patients with relapsed and refractory disease and is entering randomized clinical trials in newly diagnosed patients. The addition of monoclonal antibody therapy to chemotherapy in adults promises to enhance outcomes while hopefully not increasing toxicity. After many years of stagnation, it appears that the therapy of adults with ALL is showing significant improvement.Keywords: acute lymphoblastic leukemia, chemotherapy, monoclonal antibodies, CD19, blinatumomab
Anahtar Kelimeler : acute lymphoblastic leukemia, chemotherapy, monoclonal antibodies, blinatumomab
ISSN: 2253-1556
Cilt: 2014
Sayı: 1
Sayfa: 79 - 89
Sınıflandırma :
24
Emerging options for the treatment of melanoma – focus on ipilimumab
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Roddie C , Peggs KS
Yıl :
2014
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Claire Roddie, Karl S Peggs UCL Cancer Institute, Department of Hematology, London, UK Abstract: Ipilimumab is a fully human immunoglobulin subclass G1 anticytotoxic-T-lymphocyte-antigen-4 monoclonal antibody. It has been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency for use in advanced melanoma following clear evidence of survival benefit in randomized Phase III studies. It is also under investigation as a treatment for other solid tumors such as renal cell, lung, and prostate cancers. The purported mechanism of antitumor activity of ipilimumab is through T-cell activation, and the side effect profile reflects this. Immune-related adverse events (irAEs) affect 60% of treated patients and 15% are defined as severe. Fortunately, most irAEs are reversible with early diagnosis and correct management. FDA approval of ipilimumab is dependent on the careful execution of a risk evaluation and mitigation strategy, with the aim of increasing awareness amongst patients and clinicians of the immunological risks of treatment, and providing algorithms for management of irAEs as they develop. Ipilimumab is one of the first immunotherapies to become widely available in the setting of solid tumors, and ongoing research aims to elucidate optimal dosing, optimal scheduling, and expanded access to ipilimumab as an adjuvant or maintenance therapy where appropriate. The identification of clinical correlates or biomarkers to identify those likely to benefit from this high-cost therapy is a top priority. Keywords: ipilimumab, cytotoxic-T-lymphocyte-antigen-4, advanced melanoma, metastatic, overall survival
Anahtar Kelimeler : Ipilimumab, cytotoxic T-lymphocyte antigen 4, advanced melanoma, metastatic, overall survival
ISSN: 2253-1556
Cilt: 2014
Sayı: 1
Sayfa: 67 - 78
Sınıflandırma :
25
Identification, characterization, and synthesis of peptide epitopes and a recombinant six-epitope protein for Trichomonas vaginalis serodiagnosis
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Alderete JF , Neace CJ
Yıl :
2013
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
J F Alderete, Calvin J NeaceSchool of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USAAbstract: There is a need for a rapid, accurate serodiagnostic test useful for both women and men infected by Trichomonas vaginalis, which causes the number one sexually transmitted infection (STI). Women and men exposed to T. vaginalis make serum antibody to fructose-1,6-bisphosphate aldolase (ALD), α-enolase (ENO), and glyceraldehyde-3-phosphate dehydrogenase (GAP). We identified, by epitope mapping, the common and distinct epitopes of each protein detected by the sera of women patients with trichomonosis and by the sera of men highly seropositive to the immunogenic protein α-actinin (positive control sera). We analyzed the amino acid sequences to determine the extent of identity of the epitopes of each protein with other proteins in the databanks. This approach identified epitopes unique to T. vaginalis, indicating these peptide-epitopes as possible targets for a serodiagnostic test. Individual or combinations of 15-mer peptide epitopes with low to no identity with other proteins were reactive with positive control sera from both women and men but were unreactive with negative control sera. These analyses permitted the synthesis of a recombinant His6 fusion protein of 111 amino acids with an Mr of ~13.4 kDa, which consisted of 15-mer peptides of two distinct epitopes each for ALD, ENO, and GAP. This recombinant protein was purified by affinity chromatography. This composite protein was detected by enzyme-linked immunosorbent assay (ELISA), dot blots, and immunoblots, using positive control sera from women and men. These data indicate that it is possible to identify epitopes and that either singly, in combination, or as a composite protein represent targets for a point-of-care serodiagnostic test for T. vaginalis.Keywords: diagnostics, point-of-care, targets, trichomonosis
Anahtar Kelimeler : Diagnostics, Point-of-Care, Targets, Trichomonosis
ISSN: 2253-1556
Cilt: 2013
Sayı: 1
Sayfa: 91 - 103
Sınıflandırma :
26
Emerging roles for HMGB1 protein in immunity, inflammation, and cancer
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Martinotti S , Patrone M , Ranzato E
Yıl :
2015
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Simona Martinotti, Mauro Patrone, Elia Ranzato DiSIT – Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Alessandria, Italy Abstract: High-mobility group box 1 (HMGB1) protein is a member of the highly conserved non-histone DNA binding protein family. First identified in 1973, as one of a group of chromatin-associated proteins with high acidic and basic amino acid content, it was so named for its characteristic rapid mobility in polyacrylamide gel electrophoresis. HMGB1 was later discovered to have another function. It is released from a variety of cells into the extracellular milieu to act on specific cell-surface receptors. In this latter role, HMGB1 is a proinflammatory cytokine that may contribute to many inflammatory diseases, including sepsis. Therefore, HMGB1 regulates intracellular cascades influencing immune cell functions, including chemotaxis and immune modulation. The bioactivity of the HMGB1 is determined by specific posttranslational modifications that regulate its role in inflammation and immunity. During tumor development, HMGB1 has been reported to play paradoxical roles in promoting both cell survival and death by regulating multiple signaling pathways. In this review, we focus on the role of HMGB1 in physiological and pathological responses, as well as the mechanisms by which it contributes to immunity, inflammation, and cancer progression. Keywords: alarmin, DNA replication, HMGB1, posttranslational modifications, wound repair
Anahtar Kelimeler : HMGB1, alarmin, inflammation, DNA replication, wound repair, immunity, post-translational modifications, cancer;
ISSN: 2253-1556
Cilt: 2015
Sayı: 1
Sayfa: 101 - 109
Sınıflandırma :
27
Emerging treatments in management of prostate cancer: biomarker validation and endpoints for immunotherapy clinical trial design
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Slovin SF
Yıl :
2013
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Susan F SlovinGenitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, NY, USAAbstract: The rapidly emerging field of immunotherapy and the development of novel immunologic agents that have been approved in melanoma and successfully studied in lung cancer, kidney cancer, and prostate cancer have mandated that there be uniformity in clinical trial analysis beyond conventional survival endpoints and imaging. This includes some measure of determining whether the immunologic target is hit and how the treatment has impacted on the immune system in toto. While melanoma is leading the field towards these ends, there is some doubt that not all of the recent successes with immune therapies, for example, checkpoint inhibitors, will be effective for every cancer, and that the toxicities may also be different depending on the malignancy. This review serves to elucidate the current issues facing clinical investigators who perform immunologic trials targeted at patients with prostate cancer and discusses the challenges in assessing the right immunologic endpoints to demonstrate biologic/immunologic targeting leading to clinical benefit.Keywords: sipuleucel-T, prostate-specific antigen, prostate cancer, biomarkers, monoclonal antibodies, vaccines, cellular therapy
Anahtar Kelimeler : Sipuleucel-T, prostate cancer, biomarkers, monoclonal antibodies, vaccines, cellular therapy
ISSN: 2253-1556
Cilt: 2014
Sayı: 1
Sayfa: 1 - 8
Sınıflandırma :
28
Cancer as an immune-mediated disease
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Shurin MR
Yıl :
2012
ImmunoTargets and Therapy
Yayıncı Web Sitesi
Kaydet Alıntıla
Michael R ShurinDepartments of Pathology and Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: The link between oncology and immunology has a long history and its development is forced by the necessity to develop innovative and highly efficient modalities for immunological destruction of malignant cells. The limited efficacy of surgery, chemotherapy and radiation also exemplify these issues, as these treatments do not eliminate all cancerous cells, do not address the immunosuppressive nature of the disease and can further impair the patient's immune response weakening patient's resistance to the cancer. Multidisciplinary analysis of the interaction between the immune system and cancer in preclinical and clinical settings suggests that the immune system is closely intertwined with both cancer pathogenesis and treatment. On the one hand, cancer is a manifestation of malfunctions in immunity, as malignant cells manage to escape recognition and elimination by the immune system. Chronic infections and inflammation associated with limited or polarized immune responses also contribute to carcinogenesis and tumor progression. The tumor immunoenvironment represents specific conditions and elements that support cancerous cell survival, proliferation and spreading. On the other hand, the specificity and strength of antitumor immunity is a powerful and efficient tool that can be used to recognize and destroy neoplastic cells or their supporting microenvironment. Understanding the role of the immune system in controlling and supporting tumor initiation, formation, growth and progression has crucial implications for cancer therapy and will therefore guide the future development of cancer immunotherapy and its combination with conventional therapies to achieve optimal antitumor effects in patients with different types of cancer.Keywords: tumor immunology and immunotherapy, tumor immunoenvironment, cancer, immunosuppression, regulatory immune cells
Anahtar Kelimeler : Cancer, Immunology
ISSN: 2253-1556
Cilt: 2012
Sayı: 1
Sayfa: 1 - 6
Sınıflandırma :
Biyotıp %100
Apoptoz %20
29
Immunologic special forces: anti-pathogen cytotoxic T-lymphocyte immunotherapy following hematopoietic stem cell transplantation
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Keller MD , Bollard CM
Yıl :
2014
ImmunoTargets and Therapy
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Kaydet Alıntıla
Michael D Keller, Catherine M Bollard Program for Cell Enhancement and Technologies for Immunotherapy, Sheikh Zayed Institute for Pediatric Surgical Innovation, and Center for Cancer and Immunology Research, Children’s National Health System, Washington, DC, USA Abstract: Anti-pathogen adoptive T-cell immunotherapy has been proven to be highly effective in preventing or controlling viral infections following hematopoietic stem cell transplantation. Recent advances in manufacturing protocols allow an increased number of targeted pathogens, eliminate the need for viral transduction, broaden the potential donor pool to include pathogen-naïve sources, and reduce the time requirement for production. Early studies suggest that anti-fungal immunotherapy may also have clinical benefit. Future advances include further broadening of the pathogens that can be targeted and development of T-cells with resistance to pharmacologic immunosuppression. Keywords: immunotherapy, stem cell transplantation, T-cell, virus, fungus
Anahtar Kelimeler : immunotherapy, stem cell transplantation, T cell, virus, fungus
ISSN: 2253-1556
Cilt: 2014
Sayı: 1
Sayfa: 97 - 106
Sınıflandırma :
30
Insights into the pathogenesis of Langerhans cell histiocytosis: the development of targeted therapies
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
ImmunoTargets and Therapy
Yazar(lar) :
Hutter C , Minkov M
Yıl :
2016
ImmunoTargets and Therapy
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Kaydet Alıntıla
Caroline Hutter,1,2 Milen Minkov1–3 1International LCH Study Reference Center, Children’s Cancer Research Institute, Vienna, Austria; 2St. Anna Children's Hospital, University Clinic of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria; 3Department of Pediatrics, Adolescent Medicine and Neonatology, Rudolfstiftung Hospital, Vienna, Austria Abstract: More than a century after its first description, Langerhans cell histiocytosis (LCH) still remains an intriguing disease. Considerable progress in understanding its biology has been achieved recently. Description of the V600E BRAF mutation in samples of LCH tissue in 2010 was followed by description of additional mutations, all leading to constitutive ERK activation. Current experimental data suggest that LCH is a myeloid neoplasia with inflammatory properties, yet the exact pathophysiology remains poorly understood. Disease management paradigms have changed over time, closely reflecting the evolving view of the nature of the disease. The international Histiocyte Society have conducted three prospective clinical studies on multisystem LCH since the early 1990s. The standard frontline therapy for patients with multisystem LCH based on the cumulative knowledge of those trials consists of 6–12 weeks of initial therapy (daily oral steroids and weekly vinblastine injections), followed by pulses of prednisolone/vinblastine every 3 weeks, for a total treatment duration of 12 months. A currently ongoing study (LCH-IV) with a complex design (five interventional and two observational strata) targets further reduction of mortality and morbidity by tailoring treatment intensity depending on expected risk, as well as by exploring treatment regimens for special locations. Current knowledge on LCH pathobiology opens opportunities for improvement in the patient outcome. The activating BRAF and MAP2K1 mutations collectively accounting for about 75% of the LCH population as well as the resulting constitutive activation of downstream ERK offer an opportunity for targeted treatment. Related issues (eg, finding most effective and less toxic drugs or combinations, appropriate dosage, and optimal treatment duration) must be addressed in controlled prospective trials. Additional mechanisms, such as the interactions of the mutated dendritic cell clone with other inflammatory cells and key cytokines and chemokines, still remain attractive targets for therapeutic intervention, particularly in patients with localized, less aggressive disease. Keywords: Langerhans cell histiocytosis, treatment, targeted therapy, BRAF, myeloid neoplasm
Anahtar Kelimeler : Langerhans cell histiocytosis, treatment, targeted therapy, myeloid neoplasm
ISSN: 2253-1556
Cilt: 5
Sayfa: 81 - 91
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