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CAR T-Cell

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https://www.readbyqxmd.com/read/29910620/axicabtagene-ciloleucel-kte-c19-an-anti-cd19-car-t-therapy-for-the-treatment-of-relapsed-refractory-aggressive-b-cell-non-hodgkin-s-lymphoma
#1
REVIEW
Michael D Jain, Christina A Bachmeier, Vania H Phuoc, Julio C Chavez
Adoptive T-cell immunotherapy is a rapidly growing field and is shifting the paradigm of clinical cancer treatment. Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell therapy that was initially developed at the National Cancer Institute and has recently been commercially approved by the US Food and Drug Administration for relapsed or refractory aggressive non-Hodgkin's lymphomas including diffuse large B-cell lymphoma and its variants. The ZUMA-1 Phase I and II clinical trials formed the basis of the US Food and Drug Administration approval of this product, and we discuss the particulars of the clinical trials and the pharmacology of axi-cel...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29910179/autologous-cd19-targeted-car-t-cells-in-patients-with-residual-cll-following-initial-purine-analog-based-therapy
#2
Mark B Geyer, Isabelle Rivière, Brigitte Sénéchal, Xiuyan Wang, Yongzeng Wang, Terence J Purdon, Meier Hsu, Sean M Devlin, Elizabeth Halton, Nicole Lamanna, Jurgen Rademaker, Michel Sadelain, Renier J Brentjens, Jae H Park
Patients with residual chronic lymphocytic leukemia (CLL) following initial purine analog-based chemoimmunotherapy exhibit a shorter duration of response and may benefit from novel therapeutic strategies. We and others have previously described the safety and efficacy of autologous T cells modified to express anti-CD19 chimeric antigen receptors (CARs) in patients with relapsed or refractory B cell acute lymphoblastic leukemia and CLL. Here we report the use of CD19-targeted CAR T cells incorporating the intracellular signaling domain of CD28 (19-28z) as a consolidative therapy in 8 patients with residual CLL following first-line chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab...
June 14, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29909918/advances-in-the-use-of-natural-receptor-or-ligand-based-chimeric-antigen-receptors-cars-in-haematologic-malignancies
#3
REVIEW
Joana M Murad, David J Graber, Charles L Sentman
Chimeric antigen receptors (CAR)-T cell therapy has recently made promising advances towards treatment of B-cell malignancies. This approach makes use of an antibody-derived single chain variable fragment (scFv)-based CAR to target the CD19 antigen. Currently scFvs are the most common strategy for creation of CARs, but tumor cells can also be targeted using non-antibody based approaches with designs focused on the interaction between natural receptors and their ligands. This emerging strategy has been used in unique ways to target multiple tumor types, including solid and haematological malignancies...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909917/off-the-shelf-t-cell-therapies-for-hematologic-malignancies
#4
REVIEW
Bruce J McCreedy, Vladimir V Senyukov, Kim T Nguyen
Adoptive transfer of autologous CAR-T cells can induce durable remissions in patients with relapsed/refractory hematologic malignancies. However, multiple challenges exist for manufacturing CAR-T cells from patients with advanced disease including inability to manufacture a product, disease progression or death while waiting for the CAR-T product to be available, and heterogeneity among autologous CAR-T products that contributes to unpredictable and variable clinical activity. Healthy donor T cells can provide a source for production of universal CAR-T cells when combined with gene editing to prevent expression of endogenous TCRs and avoid generation of GvHD in HLA mismatched recipients...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909916/toxicities-associated-with-immunotherapies-for-hematologic-malignancies
#5
REVIEW
Mark B Leick, Marcela V Maus
Immunotherapy has generated tremendous hope for patients with cancer that is refractory to standard approaches. Hematologic malignancies have taken the lead in harnessing the most recent advances in cell-based immunotherapies, such as CAR T cells, and some patients have achieved durable remissions. However, these T-cell-engaging therapies are associated with a new set of toxicities which need to be managed by caretakers, oncologists, nurses, and healthcare staff. In this review we provide an overview of the toxicity of some of these revolutionary agents including bispecific T cell engagers, checkpoint inhibitors, chimeric antigen receptor T-cells...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909915/cars-and-other-t-cell-therapies-for-mm-the-clinical-experience
#6
REVIEW
Sophia Danhof, Michael Hudecek, Eric L Smith
Harnessing the endogenous immune system to eliminate malignant cells has long been an intriguing approach. After considerable success in the treatment of B-cell acute lymphoblastic leukemia, chimeric antigen receptor (CAR)-modified T cells have entered early clinical evaluation in the field of multiple myeloma (MM). The choice of suitable non-CD19 target antigens is challenging and a variety of myeloma-associated surface molecules have been under preclinical investigation. Most recent clinical protocols have focused on targeting B-cell maturation antigen (BCMA), and early results are promising...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909914/car-t-cell-therapy-for-b-cell-lymphomas
#7
REVIEW
Julio C Chavez, Frederick L Locke
B-cell non-Hodgkin's lymphoma (NHLs)is a very heterogonous malignancy with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) as the most common subtypes. Standard treatment with anti-CD20 based chemoimmunotherapy is usually very effective for disease control. However a significant proportion of patients with high-risk features (double hit lymphoma, transformed lymphomas or early relapses) will become refractory to standard therapies and will have limited alternatives for cure. Adoptive therapy with chimeric antigen receptor (CAR) T-cells is a new paradigm for effective treatment of poor prognosis lymphomas...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909913/gmp-car-t-cell-production
#8
REVIEW
Adrian P Gee
The clinical success achieved using CD19-directed CAR-T cells has stimulated many academic institutions to explore the feasibility of manufacturing these, and other CAR-T cells, in-house. This article reviews the issues that must be addressed in order to achieve this goal. It includes the manufacturing infrastructure, the regulatory environment, practical aspects of production, and the costs involved.
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909912/pre-clinical-development-of-chimeric-antigen-receptor-t-cell-immunotherapy-implications-of-design-for-efficacy-and-safety
#9
REVIEW
Leena Halim, Adam Ajina, John Maher
Following the landmark approvals by the United States Food and Drug Administration, the adoptive transfer of CD19-directed chimeric antigen receptor (CAR) T-cells has now entered mainstream clinical practice for patients with chemotherapy-resistant or refractory B-cell malignancies. These approvals have followed on from a prolonged period of pre-clinical evaluation, informing the design of clinical trials that have demonstrated unprecedented efficacy in this difficult to treat patient population. However, the delivery of autologous CAR-engineered T-cell therapy is complex, costly and not without significant risk...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909911/car-t-cells-immunologic-and-cellular-therapies-in-hematologic-malignancies
#10
EDITORIAL
Renier Brentjens, Marco L Davila
No abstract text is available yet for this article.
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29908946/effects-of-cryopreservation-on-chimeric-antigen-receptor-t-cell-functions
#11
Hao Xu, Wenyue Cao, Liang Huang, Min Xiao, Yang Cao, Lei Zhao, Na Wang, Jianfeng Zhou
Chimeric antigen receptor T (CART) cell therapy has emerged as a potentially curative "drug" for cancer treatment. Cryopreservation of CART cells is necessary for their clinical application. Systematic studies on the effects of cryopreservation on the antitumor function of CART cells are lacking. Therefore, we compared the phenotypes and functions of CART cells that were cryopreserved during ex vivo expansion with those of freshly isolated populations. T cells expressing an anti-B-cell-maturation-antigen (BCMA) chimeric antigen receptor (CAR) were expanded in vitro for 10 days and then cryopreserved...
June 14, 2018: Cryobiology
https://www.readbyqxmd.com/read/29907688/correction-tem8-antxr1-specific-car-t-cells-as-a-targeted-therapy-for-triple-negative-breast-cancer
#12
(no author information available yet)
No abstract text is available yet for this article.
June 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29907589/il1-blockade-may-ameliorate-cytokine-release-syndrome
#13
(no author information available yet)
Targeting IL1 attenuates cytokine release syndrome (CRS) without affecting CAR T-cell antitumor activity.
June 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29907163/cytokine-release-syndrome
#14
REVIEW
Alexander Shimabukuro-Vornhagen, Philipp Gödel, Marion Subklewe, Hans Joachim Stemmler, Hans Anton Schlößer, Max Schlaak, Matthias Kochanek, Boris Böll, Michael S von Bergwelt-Baildon
During the last decade the field of cancer immunotherapy has witnessed impressive progress. Highly effective immunotherapies such as immune checkpoint inhibition, and T-cell engaging therapies like bispecific T-cell engaging (BiTE) single-chain antibody constructs and chimeric antigen receptor (CAR) T cells have shown remarkable efficacy in clinical trials and some of these agents have already received regulatory approval. However, along with growing experience in the clinical application of these potent immunotherapeutic agents comes the increasing awareness of their inherent and potentially fatal adverse effects, most notably the cytokine release syndrome (CRS)...
June 15, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29904021/overcoming-resistance-of-human-non-hodgkin-s-lymphoma-to-cd19-car-ctl-therapy-by-celecoxib-and-histone-deacetylase-inhibitors
#15
Antoni Xavier Torres-Collado, Ali R Jazirehi
Patients with B-cell non-Hodgkin’s lymphoma (B-NHL) who fail to respond to first-line treatment regimens or develop resistance, exhibit poor prognosis. This signifies the need to develop alternative treatment strategies. CD19-chimeric antigen receptor (CAR) T cell-redirected immunotherapy is an attractive and novel option, which has shown encouraging outcomes in phase I clinical trials of relapsed/refractory NHL. However, the underlying mechanisms of, and approaches to overcome, acquired anti-CD19CAR CD8⁺ T cells (CTL)-resistance in NHL remain elusive...
June 14, 2018: Cancers
https://www.readbyqxmd.com/read/29903928/antibody-with-infinite-affinity-for-in-vivo-tracking-of-genetically-engineered-lymphocytes
#16
Simone Krebs, Afruja Ahad, Lukas Carter, Justin Eyquem, Christian Brand, Meghan Bell, Vladimir Ponomarev, Thomas Reiner, Claude F Meares, Stephen Gottschalk, Michel Sadelain, Steven M Larson, Wolfgang Andreas Weber
There remains an urgent need for the non-invasive tracking of transfused chimeric antigen receptor (CAR) T cells to determine their biodistribution, viability, expansion, and anti-tumor functionality. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) antibody reporter 1 (DAbR1) comprises a single-chain fragment of the anti-lanthanoid-DOTA antibody 2D12.5/G54C fused to the human CD4-transmembrane domain and binds irreversibly to lanthanoid-(S)-2-(4-acrylamidobenzyl)-DOTA (AABD). The aim of this study was to investigate whether DAbR1 can be expressed on lymphocytes and used as a reporter gene as well as a suicide gene for therapy of immune-related adverse effects...
June 14, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29900044/cd133-directed-car-t-cells-for-advanced-metastasis-malignancies-a-phase-i-trial
#17
Yao Wang, Meixia Chen, Zhiqiang Wu, Chuan Tong, Hanren Dai, Yelei Guo, Yang Liu, Jianhua Huang, Haiyan Lv, Can Luo, Kai-Chao Feng, Qing-Ming Yang, Xiao-Lei Li, Weidong Han
Expressed by cancer stem cells of various epithelial cell origins, CD133 is an attractive therapeutic target for cancers. Autologous chimeric antigen receptor-modified T-cell directed CD133 (CART-133) was first tested in this trial. The anti-tumor specificity and the postulated toxicities of CART-133 were first assessed. Then, we conducted a phase I clinical study in which patients with advanced and CD133-positive tumors received CART-133 cell-infusion. We enrolled 23 patients (14 with hepatocellular carcinoma [HCC], 7 with pancreatic carcinomas, and 2 with colorectal carcinomas)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29899889/acute-myeloid-leukemia-chimeric-antigen-receptor-t-cell-immunotherapy-how-far-up-the-road-have-we-traveled
#18
REVIEW
Sarah K Tasian
Chemotherapy resistance and relapse remain significant sources of mortality for children and adults with acute myeloid leukemia (AML). Further intensification of conventional cytotoxic chemotherapy is likely not feasible due to the severity of acute and long-term side effects upon normal tissues commonly induced by these drugs. Successful development and implementation of new precision medicine treatment approaches for patients with AML, which may improve leukemia remission and diminish toxicity, is thus a major priority...
June 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29899820/pre-clinical-validation-of-b-cell-maturation-antigen-bcma-as-a-target-for-t-cell-immunotherapy-of-multiple-myeloma
#19
De-Xiu Bu, Reshma Singh, Eugene E Choi, Marco Ruella, Selene Nunez-Cruz, Keith G Mansfield, Paul Bennett, Nathanial Barton, Qilong Wu, Jiquan Zhang, Yongqiang Wang, Lai Wei, Shawn Cogan, Tucker Ezell, Shree Joshi, Kellie J Latimer, Brian Granda, William R Tschantz, Regina M Young, Heather A Huet, Celeste J Richardson, Michael C Milone
Multiple myeloma has a continued need for more effective and durable therapies. B cell maturation antigen (BCMA), a plasma cell surface antigen and member of the tumor necrosis factor (TNF) receptor superfamily, is an attractive target for immunotherapy of multiple myeloma due to its high prevalence on malignant plasma cells. The current work details the pre-clinical evaluation of BCMA expression and development of a chimeric antigen receptor (CAR) targeting this antigen using a fully human single chain variable fragment (scFv)...
May 25, 2018: Oncotarget
https://www.readbyqxmd.com/read/29899740/gmp-grade-manufacturing-of-t-cells-engineered-to-express-a-defined-%C3%AE-%C3%AE-tcr
#20
Trudy Straetemans, Guido J J Kierkels, Ruud Doorn, Koen Jansen, Sabine Heijhuurs, Joao M Dos Santos, Anna D D van Muyden, Henri Vie, Béatrice Clemenceau, Reinier Raymakers, Moniek de Witte, Zsolt Sebestyén, Jürgen Kuball
γ9δ2T cells play a critical role in daily cancer immune surveillance by sensing cancer-mediated metabolic changes. However, a major limitation of the therapeutic application of γ9δ2T cells is their diversity and regulation through innate co-receptors. In order to overcome natural obstacles of γ9δ2T cells, we have developed the concept of T cells engineered to express a defined γδT cell receptor (TEGs). This next generation of chimeric antigen receptor engineered T (CAR-T) cells not only allows for targeting of hematological but also of solid tumors and, therefore, overcomes major limitations of many CAR-T and γδT cell strategies...
2018: Frontiers in Immunology
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