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https://www.readbyqxmd.com/read/29329591/prospects-for-chimeric-antigen-receptor-modified-t-cell-therapy-for-solid-tumors
#1
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/29320890/chimeric-antigen-receptors-in-different-cell-types-new-vehicles-join-the-race
#2
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/29317339/from-clinical-proof-of-concept-to-commercialization-of-car-t-cells
#3
Boris Calmels, Bechara Mfarrej, Christian Chabannon
The development of CAR T cells currently represents an exciting opportunity to convert the already published clinical successes observed in clinical trials into commercially available efficient therapies. However, the path toward successful commercialization is still hindered by many hurdles. Here, we review such issues as: the need for structured collaborations between hospital collection and clinical facilities and industry manufacturing facilities to streamline the supply chain; necessity for uniform and efficient medical procedures to cope with severe toxicities associated with CAR T cells; and absolute need to define an economical and sustainable model for manufacturers and payers...
January 6, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29311388/chimeric-antigen-receptor-t-cell-therapy-challenges-to-bench-to-bedside-efficacy
#4
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/29301772/cd19-car-t-therapy-and-sepsis-dancing-with-the-devil
#5
Lihua E Budde, John A Zaia
No abstract text is available yet for this article.
January 4, 2018: Blood
https://www.readbyqxmd.com/read/29298689/anti-gd2-4-1bb-chimeric-antigen-receptor-t-cell-therapy-for-the-treatment-of-chinese-melanoma-patients
#6
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/29288199/comparison-of-t-cell-activities-mediated-by-human-tcrs-and-cars-that-use-the-same-recognition-domains
#7
Daniel T Harris, Marlies V Hager, Sheena N Smith, Qi Cai, Jennifer D Stone, Philipp Kruger, Melissa Lever, Omer Dushek, Thomas M Schmitt, Philip D Greenberg, David M Kranz
Adoptive T cell therapies have achieved significant clinical responses, especially in hematopoietic cancers. Two types of receptor systems have been used to redirect the activity of T cells, normal heterodimeric TCRs or synthetic chimeric Ag receptors (CARs). TCRs recognize peptide-HLA complexes whereas CARs typically use an Ab-derived single-chain fragments variable that recognizes cancer-associated cell-surface Ags. Although both receptors mediate diverse effector functions, a quantitative comparison of the sensitivity and signaling capacity of TCRs and CARs has been limited due to their differences in affinities and ligands...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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
#8
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
#9
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
#10
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/29282693/new-approaches-in-car-t-cell-immunotherapy-for-breast-cancer
#11
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
#12
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/29249304/car-t-cell-therapy-in-refractory-large-b-cell-lymphoma
#13
Robert Stirrups
No abstract text is available yet for this article.
December 14, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29248427/car-t-cells-a-systematic-review-and-mixed-methods-analysis-of-the-clinical-trial-landscape
#14
REVIEW
David Pettitt, Zeeshaan Arshad, James Smith, Tijana Stanic, Georg Holländer, David Brindley
CAR-T cells are a promising new therapy that offer significant advantages compared with conventional immunotherapies. This systematic review and clinical trial landscape identifies and critiques published CAR-T cell clinical trials and examines the critical factors required to enable CAR-T cells to become a standard therapy. A review of the literature was conducted to identify suitable studies from the MEDLINE and Ovid bibliographic databases. The literature and database searches identified 20 studies for inclusion...
November 2, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29247018/value-in-using-car-t-cells-for-dlbcl
#15
(no author information available yet)
The phase II JULIET trial suggests that the CD19-targeting CAR T-cell therapy tisagenlecleucel produces durable responses in patients with relapsed and refractory diffuse large B-cell lymphoma. Three months after the therapy, 32% of the patients showed complete responses and 6% showed partial responses. After 6 months, those rates were 30% and 7%.
December 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29247015/car-t-cell-therapy-impresses-in-multiple-myeloma
#16
(no author information available yet)
CAR T cells that target the B-cell maturation antigen produce remissions in patients with relapsed or refractory multiple myeloma. Updated results from a phase I study suggest that 94% of patients treated with the highest doses showed complete or partial remissions and high rates of progression-free survival.
December 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29241547/car-t-cells-releasing-il-18-convert-to-t-bethigh-foxo1low-effectors-that-exhibit-augmented-activity-against-advanced-solid-tumors
#17
Markus Chmielewski, Hinrich Abken
Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells has achieved remarkable efficacy in the treatment of hematopoietic malignancies. However, eradicating large solid tumors in advanced stages of the disease remains challenging. We explored augmentation of the anti-tumor immune reaction by establishing an acute inflammatory reaction. Systematic screening indicates that IL-18 polarizes CAR T cells toward T-bethigh FoxO1low effectors with an acute inflammatory response. CAR T cells engineered with inducible IL-18 release exhibited superior activity against large pancreatic and lung tumors that were refractory to CAR T cells without cytokines...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29239915/preclinical-assessment-of-car-t-cell-therapy-targeting-the-tumor-antigen-5t4-in-ovarian-cancer
#18
Gemma L Owens, Victoria E Sheard, Milena Kalaitsidou, Daniel Blount, Yatish Lad, Eleanor J Cheadle, Richard J Edmondson, Gurdeep Kooner, David E Gilham, Richard Harrop
Chimeric antigen receptor (CAR) T cells represent a novel targeted approach to overcome both quantitative and qualitative shortfalls of the host immune system relating to the detection and subsequent destruction of tumors. The identification of antigens expressed specifically on the surface of tumor cells is a critical first step in the ability to utilize CAR T cells for the treatment of cancer. The 5T4 is a tumor-associated antigen which is expressed on the cell surface of most solid tumors including ovarian cancer...
December 12, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29238707/drug-repurposing-for-the-treatment-of-acute-myeloid-leukemia
#19
REVIEW
Vibeke Andresen, Bjørn T Gjertsen
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accumulation of immature myeloid progenitor cells in the bone marrow, compromising of normal blood cell production and ultimately resulting in bone marrow failure. With a 20% overall survival rate at 5 years and 50% in the 18- to 65-year-old age group, new medicines are needed. It is proposed that development of repurposed drugs may be a part of the new therapy needed. AML is subdivided into recurrent molecular entities based on molecular genetics increasingly accessible for precision medicine...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29226797/axicabtagene-ciloleucel-car-t-cell-therapy-in-refractory-large-b-cell-lymphoma
#20
Sattva S Neelapu, Frederick L Locke, Nancy L Bartlett, Lazaros J Lekakis, David B Miklos, Caron A Jacobson, Ira Braunschweig, Olalekan O Oluwole, Tanya Siddiqi, Yi Lin, John M Timmerman, Patrick J Stiff, Jonathan W Friedberg, Ian W Flinn, Andre Goy, Brian T Hill, Mitchell R Smith, Abhinav Deol, Umar Farooq, Peter McSweeney, Javier Munoz, Irit Avivi, Januario E Castro, Jason R Westin, Julio C Chavez, Armin Ghobadi, Krishna V Komanduri, Ronald Levy, Eric D Jacobsen, Thomas E Witzig, Patrick Reagan, Adrian Bot, John Rossi, Lynn Navale, Yizhou Jiang, Jeff Aycock, Meg Elias, David Chang, Jeff Wiezorek, William Y Go
Background In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. Methods In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine...
December 10, 2017: New England Journal of Medicine
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