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Chimeric antigen therapy

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https://www.readbyqxmd.com/read/29346301/braf-and-mek-inhibitors-influence-the-function-of-reprogrammed-t-cells-consequences-for-adoptive-t-cell-therapy
#1
Jan Dörrie, Lek Babalija, Stefanie Hoyer, Kerstin F Gerer, Gerold Schuler, Lucie Heinzerling, Niels Schaft
BRAF and MEK inhibitors (BRAFi/MEKi), the standard treatment for patients with BRAFV600 mutated melanoma, are currently explored in combination with various immunotherapies, notably checkpoint inhibitors and adoptive transfer of receptor-transfected T cells. Since two BRAFi/MEKi combinations with similar efficacy are approved, potential differences in their effects on immune cells would enable a rational choice for triple therapies. Therefore, we characterized the influence of the clinically approved BRAFi/MEKi combinations dabrafenib (Dabra) and trametinib (Tram) vs...
January 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29344676/application-of-genome-editing-techniques-in-immunology
#2
REVIEW
Agata O Zych, Malgorzata Bajor, Radoslaw Zagozdzon
The idea of using the effector immune cells to specifically fight cancer has recently evolved into an exciting concept of adoptive cell therapies. Indeed, genetically engineered T cells expressing on their surface recombinant, cancer-targeted receptors have been shown to induce promising response in oncological patients. However, in addition to exogenous expression of such receptors, there is also a need for disruption of certain genes in the immune cells to achieve more potent disease-targeted actions, to produce universal chimeric antigen receptor-based therapies or to study the signaling pathways in detail...
January 17, 2018: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/29340102/the-impact-of-antibiotic-usage-on-the-efficacy-of-chemoimmunotherapy-is-contingent-on-the-source-of-tumor-reactive-t-cells
#3
Michal P Kuczma, Zhi-Chun Ding, Tao Li, Tsadik Habtetsion, Tingting Chen, Zhonglin Hao, Locke Bryan, Nagendra Singh, James N Kochenderfer, Gang Zhou
In recent years the combined use of chemotherapy and immunotherapy, collectively termed chemoimmunotherapy, has emerged as a promising treatment option for patients with cancer. Antibiotics are commonly used to reduce infection-related complications in patients undergoing chemotherapy. Intriguingly, accumulating evidence has implicated gut microbiota as a critical determinant of host antitumor immune responses, raising the question as to whether the use of broad-spectrum antibiotics would invariably diminish tumor response to chemoimmunotherapies...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29334771/development-of-anti-human-mesothelin-targeted-chimeric-antigen-receptor-car-messenger-rna-mrna-transfected-peripheral-blood-lymphocytes-carma-hmeso-for-ovarian-cancer-therapy
#4
Chien-Fu Hung, Xuequn Xu, Linhong Li, Ying Ma, Qiu Jin, Angelia Viley, Cornell Allen, Pachai Natarajan, Rama Shivakumar, Madhusudan V Peshwa, Leisha A Emens
CD19-targeted chimeric antigen receptor (CAR) engineered T/natural kill (NK)-cell therapies can result in durable clinical responses in B-cell malignancies. However, CAR-based immunotherapies have been much less successful in solid cancers, in part due to 'on-target off-tumor' toxicity related to expression of target tumor antigens on normal tissue. Based on preliminary observations of safety and clinical activity in proof-of-concept clinical trials, tumor antigen-specific messenger RNA (mRNA) CAR transfection into selected, activated, and expanded T/NK-cells may permit prospective control of 'on-target off-tumor toxicity'...
January 15, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29329591/prospects-for-chimeric-antigen-receptor-modified-t-cell-therapy-for-solid-tumors
#5
REVIEW
Erhao Zhang, Jieyi Gu, Hanmei Xu
The potential for adoptive cell immunotherapy as a treatment against cancers has been demonstrated by the remarkable response in some patients with hematological malignancies using autologous T cells endowed with chimeric antigen receptors (CARs) specific for CD19. Clinical efficacy of CAR-T cell therapy for the treatment of solid tumors, however, is rare due to physical and biochemical factors. This review focuses on different aspects of multiple mechanisms of immunosuppression in solid tumors. We characterize the current state of CAR-modified T cell therapy and summarize the various strategies to combat the immunosuppressive microenvironment of solid tumors, with the aim of promoting T cell cytotoxicity and enhancing tumor cell eradication...
January 12, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#6
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29320890/chimeric-antigen-receptors-in-different-cell-types-new-vehicles-join-the-race
#7
Dennis C Harrer, Jan Dörrie, Niels Schaft
Adoptive cellular therapy has evolved into a powerful force in the battle against cancer, holding promise for curative responses in patients with advanced and refractory tumors. Autologous T cells, reprogrammed to target malignant cells via the expression of a chimeric antigen receptor (CAR) represent the frontrunner in this approach. Tremendous clinical regressions have been achieved using CAR-T cells against a variety of cancers both in numerous preclinical studies and in several clinical trials, most notably against ALL, and resulted in a very recent FDA-approval of the first CAR-T-cell therapy...
January 10, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29311388/chimeric-antigen-receptor-t-cell-therapy-challenges-to-bench-to-bedside-efficacy
#8
REVIEW
Shivani Srivastava, Stanley R Riddell
Immunotherapy with T cells genetically modified to express chimeric Ag receptors (CARs) that target tumor-associated molecules have impressive efficacy in hematological malignancies. The field has now embraced the challenge of applying this approach to treat common epithelial malignancies, which make up the majority of cancer cases but evade immunologic attack by a variety of subversive mechanisms. In this study, we review the principles that have guided CAR T cell design and the extraordinary clinical results being achieved in B cell malignancies targeting CD19 with a single infusion of engineered T cells...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29298689/anti-gd2-4-1bb-chimeric-antigen-receptor-t-cell-therapy-for-the-treatment-of-chinese-melanoma-patients
#9
Jiayi Yu, Xiaowen Wu, Junya Yan, Huan Yu, Longwen Xu, Zhihong Chi, Xinan Sheng, Lu Si, Chuanliang Cui, Jie Dai, Meng Ma, Tianxiao Xu, Yan Kong, Jun Guo
BACKGROUND: Chimeric antigen receptor (CAR)-engineered T cells have demonstrated promising clinical efficacy in patients with B cell lymphoma. However, the application of CAR-T cell therapy in the treatment of other solid tumors has been limited. We incorporated 4-1BB into the anti-GD2 CAR-T cells to test their cytotoxicity in melanoma in vitro and in vivo. Moreover, we reported the expression of ganglioside GD2 in non-Caucasian melanoma populations for the first time, thus providing a basis for future clinical research...
January 3, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29297925/genterapi-%C3%A2-fr%C3%A3-n-id%C3%A3-till-verklighet-%C3%A3-nnu-har-f%C3%A3-patienter-behandlats-och-preparaten-%C3%A3-r-ofta-mycket-dyra-%C3%A2-men-utvecklingen-g%C3%A3-r-fort-nu
#10
Edvard Smith, Pontus Blomberg
Gene therapy - from idea to reality Gene therapy was originally proposed 45 years ago, but it is only during the last 5-10 years that significant clinical benefit has been demonstrated. Gene therapy is in most cases in the form of engineered viruses carrying a therapeutic gene. Examples of successfully treated disorders are primary immunodeficiencies and hemophilias. In some cases, gene therapy consists of genetically modified cells, such as when chimeric antigen receptors are stably introduced into T lymphocytes, and used as tumor therapy, mainly for leukemias...
December 19, 2017: Läkartidningen
https://www.readbyqxmd.com/read/29296911/developing-t-cell-therapies-for-lymphoma-without-receptor-engineering
#11
REVIEW
Melanie Grant, Catherine M Bollard
T-cell therapy has emerged from the bench for the treatment of patients with lymphoma. Responses to T-cell therapeutics are regulated by multiple factors, including the patient's immune system status and disease stage. Outside of engineering of chimeric antigen receptors and artificial T-cell receptors, T-cell therapy can be mediated by ex vivo expansion of antigen-specific T cells targeting viral and/or nonviral tumor-associated antigens. These approaches are contributing to enhanced clinical responses and overall survival...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296864/immune-tolerance-induction-by-nonmyeloablative-haploidentical-hsct-combining-t-cell-depletion-and-posttransplant-cyclophosphamide
#12
Franco Aversa, Esther Bachar-Lustig, Noga Or-Geva, Lucia Prezioso, Sabrina Bonomini, Ilenia Manfra, Alessandro Monti, Chiara Schifano, Yael Zlotnikov-Klionsky, Massimo F Martelli, Gabriella Sammarelli, Maria Sassi, Maurizio Soli, Silvia Giuliodori, Magda Benecchi, Nicola Giuliani, Frank Lohr, Silvia Pratissoli, Yair Reisner
The establishment of safe approaches to attain durable donor-type chimerism and immune tolerance toward donor antigens represents a major challenge in transplantation biology. Haploidentical hematopoietic stem cell transplantation (HSCT) is currently used for cancer therapy either as a T-cell-depleted megadose HSCT following myeloablative conditioning or with T-cell-replete HSCT following nonmyeloablative conditioning (NMAC) and high-dose posttransplant cyclophosphamide (PTCY). The latter approach suffers from a significant rate of chronic graft-versus-host disease (GVHD), despite prolonged immunosuppression...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295696/antibody-based-epcam-targeted-therapy-of-cancer-review-and-update
#13
Shirin Eyvazi, Safar Farajnia, Siavoush Dastmalchi, Farzad Kanipour, Habib Zarredar, Mojgan Bandehpour
Todays, after four decades of the discovery of monoclonal antibodies by Kohler and Milstein in 1975, a dozen of antibodies are used in cancer targeted therapy with different strategies. The success of these antibodies depends on the specificity of antigens expressed on the cancer cells. Epithelial cell adhesion molecule (EpCAM), a homophilic cell-cell adhesion glycoprotein is a well- known tumor antigen, which expresses on epithelial tumors and circulating tumor cells as well as cancer stem cells. The EpCAM signaling pathway is associated with proliferation, differentiation and adhesion of epithelial cancer cells...
January 1, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29288188/efficacy-and-safety-of-chimeric-antigen-receptor-t-cell-car-t-therapy-in-patients-with-haematological-and-solid-malignancies-protocol-for-a-systematic-review-and-meta-analysis
#14
Emma J M Grigor, Dean A Fergusson, Fatima Haggar, Natasha Kekre, Harold Atkins, Risa Shorr, Robert A Holt, Brian Hutton, Tim Ramsay, Matthew Seftel, Derek Jonker, Mads Daugaard, Kednapa Thavorn, Justin Presseau, Manoj M Lalu
INTRODUCTION: Patients with relapsed or refractory malignancies have a poor prognosis. Immunotherapy with chimeric antigen receptor T (CAR-T) cells redirects a patient's immune cells against the tumour antigen. CAR-T cell therapy has demonstrated promise in treating patients with several haematological malignancies, including acute B-cell lymphoblastic leukaemia and B-cell lymphomas. CAR-T cell therapy for patients with other solid tumours is also being tested. Safety is an important consideration in CAR-T cell therapy given the potential for serious adverse events, including death...
December 29, 2017: BMJ Open
https://www.readbyqxmd.com/read/29285731/therapeutic-cancer-vaccines-how-much-closer-are-we
#15
Douglas G McNeel
The promise of immune-based therapies to treat cancer has been realized over the last several years with several breakthrough therapies, including T-cell checkpoint inhibitors and chimeric antigen receptor (CAR)-T cell therapies. While cancer vaccines have been investigated for many decades, to date only one has been approved in the USA as a treatment for existing cancer. The failure of several anti-tumor vaccines in large phase III trials has led many to question their future role in cancer treatment. Trials to date have demonstrated that many cancer vaccines can elicit tumor-specific T cells, but these T cells may be insufficient to mediate substantial anti-tumor effects without concurrent blockade of tumor-resistance mechanisms...
December 28, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/29284044/long-term-persistence-and-function-of-hematopoietic-stem-cell-derived-chimeric-antigen-receptor-t-cells-in-a-nonhuman-primate-model-of-hiv-aids
#16
Anjie Zhen, Christopher W Peterson, Mayra A Carrillo, Sowmya Somashekar Reddy, Cindy S Youn, Brianna B Lam, Nelson Y Chang, Heather A Martin, Jonathan W Rick, Jennifer Kim, Nick C Neel, Valerie K Rezek, Masakazu Kamata, Irvin S Y Chen, Jerome A Zack, Hans-Peter Kiem, Scott G Kitchen
Chimeric Antigen Receptor (CAR) T-cells have emerged as a powerful immunotherapy for various forms of cancer and show promise in treating HIV-1 infection. However, significant limitations are persistence and whether peripheral T cell-based products can respond to malignant or infected cells that may reappear months or years after treatment remains unclear. Hematopoietic Stem/Progenitor Cells (HSPCs) are capable of long-term engraftment and have the potential to overcome these limitations. Here, we report the use of a protective CD4 chimeric antigen receptor (C46CD4CAR) to redirect HSPC-derived T-cells against simian/human immunodeficiency virus (SHIV) infection in pigtail macaques...
December 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29283058/safety-strategies-of-genetically-engineered-t-cells-in-cancer-immunotherapy
#17
Yan-Bei Ren, Shang-Jun Sun, Shuang-Yin Han
T-cell therapy using genetically engineered T cells modified with either T cell receptor or chimeric antigen receptor hold great promise for cancer immunotherapy. The concerns about its toxicities still remain despite recent successes in clinical trials. Temporal and spatial control of the engineered therapeutic T cells may improve the safety profile of these treatment regimens. To achieve these goals, numerous approaches have been tested and utilized including the incorporation of a suicide gene, the switch-mediated activation, the combinatorial antigen recognition, etc...
December 27, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29282693/new-approaches-in-car-t-cell-immunotherapy-for-breast-cancer
#18
Jinghua Wang, Penghui Zhou
Despite significant advances in surgery, chemotherapy, radiotherapy, endocrine therapy, and molecular-targeted therapy, breast cancer remains the leading cause of death from malignant tumors among women. Immunotherapy has recently become a critical component of breast cancer treatment with encouraging activity and mild safety profiles. CAR-T therapy using genetically modifying T cells with chimeric antigen receptors (CAR) is the most commonly used approach to generate tumor-specific T cells. It has shown good curative effect for a variety of malignant diseases, especially for hematological malignancies...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29276275/chimeric-antigen-receptor-t-cell-therapy-for-lymphomas
#19
Benjamin Jolley, Scot Walker
It is estimated that 2.1% of the population of the United States will develop non-Hodgkin lymphoma (NHL) in a lifetime. With treatment, 71% of patients with NHL live to 5 years. Because current drugs used for treatment do not cure all patients and cause serious adverse effects, new strategies have been studied to treat lymphoma. One new pharmacologic strategy is to use chimeric antigen receptor T-cell (CAR T-cell) therapy. CAR T-cell therapies are very potent. As a class, the CAR T-cell therapies have induced complete remission in 50% to 80% of patients...
July 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/29275833/efficacy-against-human-prostate-cancer-by-prostate-specific-membrane-antigen-specific-transforming-growth-factor-%C3%AE-insensitive-genetically-targeted-cd8-t-cells-derived-from-patients-with-metastatic-castrate-resistant-disease
#20
Qiang Zhang, Brian T Helfand, Benedito A Carneiro, Weijun Qin, Ximing J Yang, Chung Lee, Weipeng Zhang, Francis J Giles, Massimo Cristofanilli, Timothy M Kuzel
Current immunotherapy has limited efficacy on metastatic castrate-resistant prostate cancer (mCRPC). We therefore sought to improve the antitumor ability of mCRPC patient-derived CD8+ T-cells by the endowment of specificity to prostate-specific membrane antigen (PSMA) and insensitivity to immunosuppressant molecule transforming growth factor-β (TGF-ß) under the control of herpes simplex virus-1 thymidine kinase. CD8+ T-cells were collected by leukapheresis and cultured in a Food and Drug Administration-approved Cell Processing Work Station...
December 21, 2017: European Urology
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