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Chimeric antigen receptor

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https://www.readbyqxmd.com/read/28935694/cellular-kinetics-of-ctl019-in-relapsed-refractory-b-cell-acute-lymphoblastic-leukemia-and-chronic-lymphocytic-leukemia
#1
Karen Thudium Mueller, Shannon L Maude, David L Porter, Noelle Frey, Patricia Wood, Xia Han, Edward Waldron, Abhijit Chakraborty, Rakesh Awasthi, Bruce L Levine, J Joseph Melenhorst, Stephan A Grupp, Carl H June, Simon F Lacey
Tisagenlecleucel (CTL019) is an investigational immunotherapy that involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells. We previously reported that CTL019 achieved impressive clinical efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), including the expansion and persistence of CTL019 cells, which correlates with response to therapy. Here, we performed formal cellular kinetic analyses of CTL019 in a larger cohort of 103 patients treated with CTL019 in 2 different diseases (ALL and CLL)...
September 21, 2017: Blood
https://www.readbyqxmd.com/read/28932644/romidepsin-alone-or-in-combination-with-anti-cd20-chimeric-antigen-receptor-expanded-natural-killer-cells-targeting-burkitt-lymphoma-in-vitro-and-in-immunodeficient-mice
#2
Yaya Chu, Ashlin Yahr, Brian Huang, Janet Ayello, Matthew Barth, Mitchell S Cairo
Facilitating the development of alternative targeted therapeutic strategies is urgently required to improve outcome or circumvent chemotherapy resistance in children, adolescents, and adults with recurrent/refractory de novo mature B-cell (CD20) non-Hodgkin lymphoma, including Burkitt lymphoma (BL). Romidepsin, a histone deacetylase inhibitor (HDACi), has been used to treat cutaneous T-cell lymphoma. We have demonstrated the significant anti-tumor effect of anti-CD20 chimeric antigen receptor (CAR) modified expanded peripheral blood natural killer (exPBNK) against rituximab-sensitive and -resistant BL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931402/recent-advances-of-bispecific-antibodies-in-solid-tumors
#3
REVIEW
Shengnan Yu, Anping Li, Qian Liu, Xun Yuan, Hanxiao Xu, Dechao Jiao, Richard G Pestell, Xinwei Han, Kongming Wu
Cancer immunotherapy is the most exciting advancement in cancer therapy. Similar to immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T), bispecific antibody (BsAb) is attracting more and more attention as a novel strategy of antitumor immunotherapy. BsAb not only offers an effective linkage between therapeutics (e.g., immune effector cells, radionuclides) and targets (e.g., tumor cells) but also simultaneously blocks two different oncogenic mediators. In recent decades, a variety of BsAb formats have been generated...
September 20, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28928126/chimeric-antigen-receptor-t-cell-therapies-for-multiple-myeloma
#4
Lekha Mikkilineni, James N Kochenderfer
Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T-cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR T-cells against leukemia and lymphoma has encouraged development of CAR T-cell therapies for MM...
September 19, 2017: Blood
https://www.readbyqxmd.com/read/28925994/chimeric-antigen-receptor-t-cell-therapy-assessment-and-management-of-toxicities
#5
REVIEW
Sattva S Neelapu, Sudhakar Tummala, Partow Kebriaei, William Wierda, Cristina Gutierrez, Frederick L Locke, Krishna V Komanduri, Yi Lin, Nitin Jain, Naval Daver, Jason Westin, Alison M Gulbis, Monica E Loghin, John F de Groot, Sherry Adkins, Suzanne E Davis, Katayoun Rezvani, Patrick Hwu, Elizabeth J Shpall
Immunotherapy using T cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH)...
September 19, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28924019/kinetics-and-biomarkers-of-severe-cytokine-release-syndrome-after-cd19-chimeric-antigen-receptor-modified-t-cell-therapy
#6
Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, Juliane Gust, W Conrad Liles, Mark M Wurfel, José A López, Junmei Chen, Dominic Chung, Susanna Harju-Baker, Sindhu Cherian, Xueyan Chen, Stanley R Riddell, David G Maloney, Cameron J Turtle
Lymphodepletion chemotherapy followed by infusion of CD19-specific chimeric antigen receptor-modified T cells (CAR-T) has produced impressive antitumor responses in patients with refractory CD19(+) B cell malignancies, but is often associated with cytokine release syndrome (CRS). Our understanding of CRS continues to evolve, and identification of the kinetics of CRS and predictive clinical and laboratory biomarkers of severity are needed to evaluate strategies to mitigate toxicity. We report the clinical presentation and identify biomarkers of severe CRS in 133 adult patients who received CD19 CAR-T cells...
September 18, 2017: Blood
https://www.readbyqxmd.com/read/28923441/car-t-cell-immunotherapy-in-hematology-and-beyond
#7
Claudia Rossig
Chimeric T cell receptors (CARs) combine extracellular antigen recognition domains and T cell activation components in single molecules. CAR gene transfer thereby allows to generate T cells with engineered specificities. The translational development of CAR-based T cell therapies is most advanced in B cell cancers where CAR-engineered T cells against the B lineage antigen CD19 have generated impressive results in early clinical trials. CARs are now also explored as tools to eliminate autoreactive B cell clones and to engineer T cells with immunosuppressive function for preventing pathological auto- or alloresponses...
September 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28920716/transposons-moving-forward-from-preclinical-studies-to-clinical-trials
#8
Jaitip Tipanee, Thierry VandenDriessche, Marinee K Chuah
Transposons have emerged as promising vectors for gene therapy that can potentially overcome some of the limitations of commonly used viral vectors. Transposons stably integrate into the target cell genome, enabling persistent expression of therapeutic genes. Transposons have evolved from being used as basic tools in biomedical research to bona fide therapeutics. Currently, the most promising transposons for gene therapy applications are derived from Sleeping Beauty (SB) or piggyBac (PB). Stable transposition requires co-delivery of the transposon DNA with the corresponding transposase gene, mRNA, or protein...
August 22, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28919377/combination-cancer-therapy-using-chimeric-antigen-receptor-engineered-natural-killer-cells-as-drug-carriers
#9
Elizabeth L Siegler, Yu Jeong Kim, Xianhui Chen, Natnaree Siriwon, John Mac, Jennifer A Rohrs, Paul D Bryson, Pin Wang
The therapeutic limitations of conventional chemotherapeutic drugs include chemo-resistance, tumor recurrence, and metastasis. Numerous nanoparticle-based active targeting approaches have emerged to enhance the intracellular concentration of drugs in tumor cells; however, efficient delivery of these systems to the tumor site while sparing healthy tissue remains elusive. Recently, much attention has been given to human immune-cell-directed nanoparticle drug delivery, because immune cells can traffic to the tumor and inflammatory sites...
August 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28912137/enhanced-cancer-immunotherapy-by-chimeric-antigen-receptor-modified-t-cells-engineered-to-secrete-checkpoint-inhibitors
#10
Pin Wang, Si Li, Natnaree Siriwon, Xiaoyang Zhang, Shuai Yang, Tao Jin, Feng He, Yu Jeong Kim, John Mac, Zhengfei Lu, Sijie Wang, Xiaolu Han
PURPOSE: Despite favorable responses of CAR-engineered T cell therapy in patients with hematologic malignancies, the outcome has been far from satisfactory in the treatment of solid tumors, partially owing to the development of an immunosuppressive tumor microenvironment. To overcome this limitation, we engineered CAR-T cells secreting checkpoint inhibitors (CPIs) targeting PD-1 (CAR.αPD1-T) and evaluated their efficacy in a human lung carcinoma xenograft mouse model. EXPERIMENTAL DESIGN: To evaluate the effector function and expansion capacity of CAR...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28901790/anti-cd123-chimeric-antigen-receptor-t-cells-cart-an-evolving-treatment-strategy-for-hematological-malignancies-and-a-potential-ace-in-the-hole-against-antigen-negative-relapse
#11
Katherine D Cummins, Saar Gill
Chimeric antigen receptor-modified T-cells (CART) are a potent and targeted immunotherapy which have induced remissions in some patients with chemotherapy refractory or relapsed (RR) hematologic malignancies. Hundreds of patients have now been treated worldwide with anti-CD19 CART cells, with complete response rates of up to 90%. CART therapy has a unique toxicity profile, and unfortunately not all responses are durable. Treatment failure occurs via two main routes - by loss of the CART cell population, or relapse with antigen loss...
September 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28900984/-targeted-therapy-combined-with-immunotherapy-in-gastrointestinal-stromal-tumor-a-new-era-of-hope-and-challenges
#12
Wenyi Zhao, Hui Cao
New immunotherapy represented by immune checkpoint inhibitor therapy and chimeric antigen receptor T-Cell immunotherapy (CAR-T) has already become hot trend in the treatment of malignant tumors. In gastrointestinal stromal tumor (GIST), with notable tumor-infiltrating immune cells existing in GIST tissues and immunological effects reported in imatinib mesylate (IM) treatment, the clinicians and researchers started to realize the possibilities of immunotherapy in GIST. Recent studies reported that PD-1/PD-L1 or CTLA-4 blockade may enhance the T-cell activity and anti-tumor effect of targeted therapy, which can be applied in advanced GIST, and anti-KIT CAR T-cells indicated a new immunotherapeutic targeted strategy for GIST patients with TKI resistance...
September 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28895856/gene-modified-t-cell-therapies-for-hematological-malignancies
#13
REVIEW
Ulrike Abramowski-Mock, Juliette M Delhove, Waseem Qasim
This article focuses on clinical applications of T cells transduced to express recombinant T cell receptor and chimeric antigen receptor constructs directed toward hematological malignancies, and considers newer strategies incorporating gene-editing technologies to address GvHD and host-mediated rejection. Recent data from clinical trials are reviewed, and an overview is provided of current and emerging manufacturing processes; consideration is also given to new developments in the pipeline.
October 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28888074/early-recovery-of-circulating-immature-b-cells-in-b-lymphoblastic-leukemia-patients-after-cd19-targeted-car-t-cell-therapy-a-pitfall-for-minimal-residual-disease-detection
#14
Wenbin Xiao, Dalia Salem, Catherine McCoy, Daniel Lee, Nirali N Shah, Maryalice Stetler-Stevenson, Constance M Yuan
BACKGROUND: CD19-targeted chimeric-antigen receptor-modified T-cells (CAR-T) are promising in the treatment of refractory B-lymphoblastic leukemia (B-ALL). Minimal residual disease (MRD) detection by multicolor flow cytometry (FCM) is critical to distinguish B-ALL MRD from regenerating, non-neoplastic B-cell populations. METHODS: FCM was performed on samples from 9 patients with B-ALL treated with CAR-T. RESULTS: All 9 patients showed response to CAR-T...
September 9, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28887358/first-ever-car-t-cell-therapy-approved-in-u-s
#15
(no author information available yet)
The first chimeric antigen receptor T-cell therapy, tisagenlecleucel, received FDA approval for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia who haven't responded to standard therapy or who have relapsed at least twice.
September 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28885562/human-cd3-t-cells-with-the-anti-erbb2-chimeric-antigen-receptor-exhibit-efficient-targeting-and-induce-apoptosis-in-erbb2-overexpressing-breast-cancer-cells
#16
Rusheni Munisvaradass, Suresh Kumar, Chandramohan Govindasamy, Khalid S Alnumair, Pooi Ling Mok
Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition...
September 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28880983/chimeric-antigen-receptor-car-t-cell-therapy
#17
John M Pagel, Howard Jack West
No abstract text is available yet for this article.
September 7, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28880014/chimeric-antigen-receptor-car-transduced-natural-killer-cells-in-tumor-immunotherapy
#18
REVIEW
Yuan Hu, Zhi-Gang Tian, Cai Zhang
Natural killer (NK) cells are potential effector cells in cell-based cancer immunotherapy, particularly in the control of hematological malignancies. The chimeric antigen receptor (CAR) is an artificially modified fusion protein that consists of an extracellular antigen recognition domain fused to an intracellular signaling domain. T cells genetically modified with a CAR have demonstrated remarkable success in the treatment of hematological cancers. Compared to T cells, CAR-transduced NK cells (CAR-NK) exhibit several advantages, such as safety in clinical use, the mechanisms by which they recognize cancer cells, and their abundance in clinical samples...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28878363/a-tcr-based-chimeric-antigen-receptor
#19
Even Walseng, Hakan Köksal, Ibrahim M Sektioglu, Anne Fåne, Gjertrud Skorstad, Gunnar Kvalheim, Gustav Gaudernack, Else Marit Inderberg, Sébastien Wälchli
Effector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods have emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although very potent, CAR recognition is limited to membrane antigens which represent around 1% of the total proteins expressed, whereas TCRs have the advantage of targeting any peptide resulting from cellular protein degradation. However, TCRs depend on heavy signalling machinery only present in T cells which restricts the type of eligible therapeutic cells...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877899/equipping-nk-cells-with-cars
#20
(no author information available yet)
Adding a chimeric antigen receptor (CAR) to natural killer (NK) cells is garnering interest as a therapeutic strategy because this immune cell type doesn't cause graft-versus-host disease, making its widespread, off-the-shelf use feasible. Based on promising preclinical data, a phase I/II trial of one such CAR NK-cell therapy is under way, targeting CD19 in hematologic malignancies.
September 6, 2017: Cancer Discovery
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