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https://www.readbyqxmd.com/read/28820501/interleukin-armed-chimeric-antigen-receptor-modified-t-cells-for-cancer-immunotherapy
#1
REVIEW
Y Huang, D Li, D-Y Qin, H-F Gou, W Wei, Y-S Wang, Y-Q Wei, W Wang
Chimeric antigen receptor-modified T cells (CAR-T) are endowed with cytotoxic specificity to tumor cells. Although CAR-T-based cancer immunotherapy presents curable therapeutic potential for hematological malignancies, achieving substantial efficacy for solid tumors remain challenging. Researchers have exploited many strategies to enhance the anti-tumor efficacy of CAR-T cells for solid tumors, among which cytokine-armed CAR-T cells improve the proliferation, survival, homing and other properties of CAR-T cells...
August 18, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28810803/driving-cars-on-the-highway-to-solid-cancer-some-considerations-on-the-adoptive-therapy-with-car-t-cells
#2
Hinrich Abken
Adoptive therapy with chimeric antigen receptor (CAR) redirected T cells achieved lasting remissions in hematologic malignancies even in terminal stages of the disease; exploring CAR T cell therapy in the treatment of solid tumors has just begun, balancing efficacy versus toxicity in early phase trials. In contrast to leukemia/lymphoma, solid tumors display a tremendously variable biology demanding different strategies to make a T cell attack successful in the long-term. We summarize current developments, discuss the hurdles and consider some modifications to improve the CAR T cell therapy in the treatment of solid tumors...
August 16, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28808046/car-t-cells-drive-cll-remissions
#3
(no author information available yet)
A new study shows that chimeric antigen receptor T cells produce objective responses in 71% of patients with chronic lymphocytic leukemia whose disease progressed despite receiving ibrutinib or who are unable to tolerate the drug. Cancer cells were undetectable in the bone marrow in 81% of tested patients, and 64% of tested patients showed complete lymph node responses. Most patients experienced adverse effects, however.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28807568/function-of-novel-anti-cd19-chimeric-antigen-receptors-with-human-variable-regions-is-affected-by-hinge-and-transmembrane-domains
#4
Leah Alabanza, Melissa Pegues, Claudia Geldres, Victoria Shi, Jed J W Wiltzius, Stuart A Sievers, Shicheng Yang, James N Kochenderfer
Anti-CD19 chimeric antigen receptor (CAR) T cells have caused remissions of B cell malignancies, but problems including cytokine-mediated toxicity and short persistence of CAR T cells in vivo might limit the effectiveness of anti-CD19 CAR T cells. Anti-CD19 CARs that have been tested clinically had single-chain variable fragments (scFvs) derived from murine antibodies. We have designed and constructed novel anti-CD19 CARs containing a scFv with fully human variable regions. T cells expressing these CARs specifically recognized CD19(+) target cells and carried out functions including degranulation, cytokine release, and proliferation...
July 27, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28805662/clinical-and-immunological-responses-after-cd30-specific-chimeric-antigen-receptor-redirected-lymphocytes
#5
Carlos A Ramos, Brandon Ballard, Huimin Zhang, Olga Dakhova, Adrian P Gee, Zhuyong Mei, Mrinalini Bilgi, Meng-Fen Wu, Hao Liu, Bambi Grilley, Catherine M Bollard, Bill H Chang, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop, Gianpietro Dotti, Barbara Savoldo
BACKGROUND: Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS: We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28804691/combination-of-celecoxib-celebrex-%C3%A2-and-cd19-car-redirected-ctl-immunotherapy-for-the-treatment-of-b-cell-non-hodgkin-s-lymphomas
#6
REVIEW
Tam Nm Dinh, Alexandra S Onea, Ali R Jazirehi
The nonsteroidal anti-inflammatory drug (NSAID) Celecoxib (Celebrex(®)) received Food and Drug Administration (FDA) approval in 1998 for treatment of osteoarthritis and rheumatoid arthritis, and in recent years, its use has been extended to various types of malignancies, such as breast, colon, and urinary cancers. To maintain the survival of malignant B cells, non-Hodgkin's Lymphoma (NHL) is highly dependent on inflammatory microenvironment, and is inhibited by celecoxib. Celecoxib hinders tumor growth interacting with various apoptotic genes, such as cyclooxygenase-2 (Cox-2), B-cell lymphoma 2 (Bcl-2) family, phosphor-inositide-3 kinase/serine-threonine-specific protein kinase (PI3K/Akt), and inhibitors of apoptosis proteins (IAP) family...
2017: American Journal of Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28803861/long-duration-complete-remissions-of-diffuse-large-b-cell-lymphoma-after-anti-cd19-chimeric-antigen-receptor-t%C3%A2-cell-therapy
#7
James N Kochenderfer, Robert P T Somerville, Tangying Lu, James C Yang, Richard M Sherry, Steven A Feldman, Lori McIntyre, Adrian Bot, John Rossi, Norris Lam, Steven A Rosenberg
T cells expressing anti-CD19 chimeric antigen receptors (CARs) can induce complete remissions (CRs) of diffuse large B cell lymphoma (DLBCL). The long-term durability of these remissions is unknown. We administered anti-CD19 CAR T cells preceded by cyclophosphamide and fludarabine conditioning chemotherapy to patients with relapsed DLBCL. Five of the seven evaluable patients obtained CRs. Four of the five CRs had long-term durability with durations of remission of 56, 51, 44, and 38 months; to date, none of these four cases of lymphomas have relapsed...
July 13, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28801306/inducible-activation-of-myd88-and-cd40-in-car-t-cells-results-in-controllable-and-potent-antitumor-activity-in-preclinical-solid-tumor-models
#8
Melinda Mata, Claudia Gerken, Phuong Nguyen, Giedre Krenciute, David M Spencer, Stephen Gottschalk
Adoptive immunotherapy with T-cells expressing chimeric antigen receptors (CARs) has had limited success for solid tumors in early phase clinical studies. We reasoned that introducing into CAR T-cells an inducible co-stimulatory (iCO) molecule consisting of a chemical inducer of dimerization (CID)-binding domain and the MyD88 and CD40 signaling domains would improve and control CAR T-cell activation. In the presence of CID, T-cells expressing HER2-CARζ and a MyD88/CD40-based iCO molecule (HER2ζ.iCO T-cells) had superior T-cell proliferation, cytokine production, and ability to sequentially kill targets in vitro relative to HER2ζ...
August 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28799547/immunotherapy-car-t-cells-in-glioblastoma
#9
Crunkhorn Sarah
No abstract text is available yet for this article.
August 11, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28796529/designed-ankyrin-repeat-proteins-as-her2-targeting-domains-in-chimeric-antigen-receptor-engineered-t-cells
#10
Elizabeth Siegler, Si Li, Yu Jeong Kim, Pin Wang
Chimeric antigen receptor (CAR) engineering is a branch of cancer immunotherapy that equips immune cells to target tumor antigens expressed on the cell surface using antibody-derived single-chain variable fragments (scFvs). However, other antibody mimetics, such as designed ankyrin repeat proteins (DARPins), can also serve as antigen-binding domains in CARs. This study shows that CAR-engineered T (CAR-T) cells utilizing Her2-targeting DARPins G3 and 929 can target human epidermal growth factor receptor 2 (Her2)-overexpressing cancer cells as effectively as CAR-T cells with the scFv 4D5 in vitro, and G3 CAR-T cells can slow or eliminate tumor growth in vivo as effectively as 4D5 CAR-T cells...
June 22, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28771105/nk-92-cell-another-ideal-carrier-for-chimeric-antigen-receptor
#11
Wan-Ning Wang, Guang-Yu Zhou, Wen-Long Zhang
The remarkable clinical outcomes of the treatment for B-cell malignancies through the application of CD19 chimeric antigen receptor T (CAR-T) cells have made adoptive immunotherapy with genetically modified immune effector cells a hotspot in the field of antitumor. However, numerous toxicities of CAR-T cells have been identified. Thus, some studies have resorted to another cytotoxic cell, NK-92 cell, to reach for better efficacy with minimal toxicity. Preclinical studies have confirmed the safety and feasibility of the genetically modified NK-92 cells with highly specific cytotoxicity in vitro and in vivo...
August 3, 2017: Immunotherapy
https://www.readbyqxmd.com/read/28771104/-atypical-car-t-cells-nkg2d-and-erb-b-as-examples-of-natural-receptor-ligands-to-target-recalcitrant-solid-tumors
#12
David E Gilham, John Maher
Chimeric antigen receptor (CAR) T-cell therapy has recently been recommended for approval for certain B-cell malignancies bringing the approach closer to mainstream cancer treatment. This rapid rise to prominence has been driven by impressive clinical results and the means to successfully commercialize the approach now being actively pursued. The current success of CAR T cells in B-cell malignancies relies upon the absolute lineage specificity of the CD19 antigen. CARs can also be targeted using non-antibody approaches, including the use of receptors and ligands to provide target specificity that have different specificities and binding kinetics...
August 3, 2017: Immunotherapy
https://www.readbyqxmd.com/read/28771103/overcoming-barriers-of-car-t-cell-therapy-in-patients-with-mesothelin-expressing-cancers
#13
Mark H O'Hara, Caitlin Stashwick, Gabriela Plesa, Janos L Tanyi
One obstacle to the application of immunotherapy to solid malignancies is to overcome the existing tolerance to self-antigens. Vaccine strategies aimed at harnessing endogenous antitumor T cells are limited by the T-cell receptor repertoire, which can be detected within the thymus as central tolerance or rendered nonfunctional by post-thymic mechanisms of peripheral tolerance. Adoptive immunotherapy can overcome these obstacles, since therapeutically effective T cells can be engineered to recognize tumors. Continued advancements in novel treatments, including immunotherapy, in solid malignancies are imperative...
August 3, 2017: Immunotherapy
https://www.readbyqxmd.com/read/28765509/editorial-teaching-old-car-t-cells-new-tricks
#14
EDITORIAL
Lindsey M Kuehm, Ryan M Teague
No abstract text is available yet for this article.
August 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28765140/clinical-development-of-car-t-cells-challenges-and-opportunities-in-translating-innovative-treatment-concepts
#15
REVIEW
Jessica Hartmann, Martina Schüßler-Lenz, Attilio Bondanza, Christian J Buchholz
Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint inhibition, has been celebrated as a breakthrough technology due to the substantial benefit observed in clinical trials with patients suffering from relapsed or refractory B-cell malignancies. In this review, we provide a comprehensive overview of the clinical trials performed so far worldwide and analyze parameters such as targeted antigen and indication, CAR molecular design, CAR T cell manufacturing, anti-tumor activities, and related toxicities...
August 1, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28764981/promises-and-limitations-of-nanoparticles-in-the-era-of-cell-therapy-example-with-cd19-targeting-chimeric-antigen-receptor-car-modified-t-cells
#16
Hélène Jakobczyk, Flavien Sciortino, Soizic Chevance, Fabienne Gauffre, Marie-Bérengère Troadec
A number of nanoparticles has been developed by chemists for biomedical applications to meet imaging and targeting needs. In parallel, adoptive T therapy with chimeric antigen receptor engineered T cells (CART cells) has recently held great promise in B-cell malignancy treatments thanks to the development of anti-CD19 CAR T cells. Indeed, CD19 is a reliable B cell marker and a validated target protein for therapy. In this perspective article, we propose to discuss the advantages, limits and challenges of nanoparticles and CAR T cells, focusing on CD19 targeting objects: anti-CD19 nanoparticles and anti-CD19 CAR T cells, because those genetically-modified cells are the most widely developed in clinical setting...
July 29, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28762387/haematological-cancer-after-ibrutinib-car-t-cells-induce-responses
#17
Diana Romero
No abstract text is available yet for this article.
August 1, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28762313/adoptive-immunotherapy-for-b-cell-malignancies-using-cd19-targeted-chimeric-antigen-receptor-t-cells-a-systematic-review-of-efficacy-and-safety
#18
Lu Hao, Tongtong Li, Lung-Ji Chang, Xiaochuan Chen
BACKGROUND: Adoptive infusion of chimeric antigen receptor transduced T-cells (CAR-T) is a powerful tool of immunotherapy for hematological malignancies, as evidenced by recently published and unpublished clinical results. OBJECTIVE: In this report, we performed a meta-analysis to evaluate the efficacy and side effects of CAR-T on relapsed B-cell malignancies, including leukemia and lymphoma. METHODS: Clinical studies investigating efficacy and safety of CAR-T in acute and chronic lymphocytic leukemia and lymphoma were identified by searching PubMed and EMBASE...
August 1, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28755873/chimeric-antigen-receptor-t-cell-therapy-for-glioblastoma
#19
REVIEW
Analiz Rodriguez, Christine Brown, Behnam Badie
Chimeric antigen receptor (CAR) T-cell therapy has shown great promise in the treatment of hematological disease, and its utility for treatment of solid tumors is beginning to unfold. Glioblastoma continues to portend a grim prognosis and immunotherapeutic approaches are being explored as a potential treatment strategy. Identification of appropriate glioma-associated antigens, barriers to cell delivery, and presence of an immunosuppressive microenvironment are factors that make CAR T-cell therapy for glioblastoma particularly challenging...
July 15, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28755872/new-approaches-for-the-enhancement-of-chimeric-antigen-receptors-for-the-treatment-of-hiv
#20
REVIEW
Mayra A Carrillo, Anjie Zhen, Jerome A Zack, Scott G Kitchen
HIV infection continues to be a life-long chronic disease in spite of the success of antiretroviral therapy (ART) in controlling viral replication and preventing disease progression. However, because of the high cost of treatment, severe side effects, and inefficiency in curing the disease with ART, there is a call for alternative therapies that will provide a functional cure for HIV. Cytotoxic T lymphocytes (CTLs) are vital in the control and clearance of viral infections and therefore immune-based therapies have attempted to engineer HIV-specific CTLs that would be able to clear the infection from the body...
July 14, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
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