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CAR T cell

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9 papers 100 to 500 followers Fascinating futuristic stuff!
By Faye Kehler Family Physician and GP Anesthetist since 1987 interested in all aspects of Medicine
Saad Sirop Kenderian, Marco Ruella, Saar Gill, Michael Kalos
Several decades of humoral immunotherapy using monoclonal antibodies and cellular immunotherapy using hematopoietic cell transplantation have recently culminated in a successful merger: the development and clinical application of genetically engineered antibody-T cell chimeras. Also known as chimeric antigen receptor T cells (CAR T cells), these entities combine the exquisite antigen specificity of antibodies with the polyfunctionality and potency of cellular immunity and are a prime example of the potential for synthetic biology to treat disease...
November 15, 2014: Cancer Research
James N Kochenderfer, Mark E Dudley, Sadik H Kassim, Robert P T Somerville, Robert O Carpenter, Maryalice Stetler-Stevenson, James C Yang, Giao Q Phan, Marybeth S Hughes, Richard M Sherry, Mark Raffeld, Steven Feldman, Lily Lu, Yong F Li, Lien T Ngo, Andre Goy, Tatyana Feldman, David E Spaner, Michael L Wang, Clara C Chen, Sarah M Kranick, Avindra Nath, Debbie-Ann N Nathan, Kathleen E Morton, Mary Ann Toomey, Steven A Rosenberg
PURPOSE: T cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous anti-CD19 CAR T cells to patients with advanced CD19(+) B-cell malignancies. PATIENTS AND METHODS: We treated 15 patients with advanced B-cell malignancies. Nine patients had diffuse large B-cell lymphoma (DLBCL), two had indolent lymphomas, and four had chronic lymphocytic leukemia. Patients received a conditioning chemotherapy regimen of cyclophosphamide and fludarabine followed by a single infusion of anti-CD19 CAR T cells...
February 20, 2015: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
John H Sampson, Bryan D Choi, Luis Sanchez-Perez, Carter M Suryadevara, David J Snyder, Catherine T Flores, Robert J Schmittling, Smita K Nair, Elizabeth A Reap, Pamela K Norberg, James E Herndon, Chien-Tsun Kuan, Richard A Morgan, Steven A Rosenberg, Laura A Johnson
PURPOSE: Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed in both tumors and normal tissues have led to significant toxicity. Preclinical studies have been limited by the use of xenograft models that do not adequately recapitulate the immune system of a clinically relevant host. A constitutively activated mutant of the naturally occurring epidermal growth factor receptor (EGFRvIII) is antigenically identical in both human and mouse glioma, but is also completely absent from any normal tissues...
February 15, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Eleanor J Cheadle, Hannah Gornall, Vania Baldan, Vivien Hanson, Robert E Hawkins, David E Gilham
Blockbuster antibody therapies have catapulted immune-based approaches to treat cancer into the consciousness of mainstay clinical research. On the back of this, other emerging immune-based therapies are providing great promise. T-cell therapy is one such area where recent trials using T cells genetically modified to express an antibody-based chimeric antigen receptor (CAR) targeted against the CD19 antigen have demonstrated impressive responses when adoptively transferred to patients with advanced chronic lymphocytic leukemia...
January 2014: Immunological Reviews
Markus Chmielewski, Andreas A Hombach, Hinrich Abken
Adoptive T-cell therapy recently achieved impressive efficacy in early phase trials, in particular in hematologic malignancies, strongly supporting the notion that the immune system can control cancer. A current strategy of favor is based on ex vivo-engineered patient T cells, which are redirected by a chimeric antigen receptor (CAR) and recognize a predefined target by an antibody-derived binding domain. Such CAR T cells can substantially reduce the tumor burden as long as the targeted antigen is present on the cancer cells...
January 2014: Immunological Reviews
James N Kochenderfer, Mark E Dudley, Robert O Carpenter, Sadik H Kassim, Jeremy J Rose, William G Telford, Frances T Hakim, David C Halverson, Daniel H Fowler, Nancy M Hardy, Anthony R Mato, Dennis D Hickstein, Juan C Gea-Banacloche, Steven Z Pavletic, Claude Sportes, Irina Maric, Steven A Feldman, Brenna G Hansen, Jennifer S Wilder, Bazetta Blacklock-Schuver, Bipulendu Jena, Michael R Bishop, Ronald E Gress, Steven A Rosenberg
New treatments are needed for B-cell malignancies persisting after allogeneic hematopoietic stem cell transplantation (alloHSCT). We conducted a clinical trial of allogeneic T cells genetically modified to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. T cells for genetic modification were obtained from each patient's alloHSCT donor. All patients had malignancy that persisted after alloHSCT and standard donor lymphocyte infusions (DLIs). Patients did not receive chemotherapy prior to the CAR T-cell infusions and were not lymphocyte depleted at the time of the infusions...
December 12, 2013: Blood
Conrad Russell Y Cruz, Kenneth P Micklethwaite, Barbara Savoldo, Carlos A Ramos, Sharon Lam, Stephanie Ku, Oumar Diouf, Enli Liu, A John Barrett, Sawa Ito, Elizabeth J Shpall, Robert A Krance, Rammurti T Kamble, George Carrum, Chitra M Hosing, Adrian P Gee, Zhuyong Mei, Bambi J Grilley, Helen E Heslop, Cliona M Rooney, Malcolm K Brenner, Catherine M Bollard, Gianpietro Dotti
Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity...
October 24, 2013: Blood
Liza B John, Christel Devaud, Connie P M Duong, Carmen S Yong, Paul A Beavis, Nicole M Haynes, Melvyn T Chow, Mark J Smyth, Michael H Kershaw, Phillip K Darcy
PURPOSE: To determine the antitumor efficacy and toxicity of a novel combination approach involving adoptive T-cell immunotherapy using chimeric antigen receptor (CAR) T cells with an immunomodulatory reagent for blocking immunosuppression. EXPERIMENTAL DESIGN: We examined whether administration of a PD-1 blocking antibody could increase the therapeutic activity of CAR T cells against two different Her-2(+) tumors. The use of a self-antigen mouse model enabled investigation into the efficacy, mechanism, and toxicity of this combination approach...
October 15, 2013: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Robert O Carpenter, Moses O Evbuomwan, Stefania Pittaluga, Jeremy J Rose, Mark Raffeld, Shicheng Yang, Ronald E Gress, Frances T Hakim, James N Kochenderfer
PURPOSE: Multiple myeloma is a usually incurable malignancy of plasma cells. New therapies are urgently needed for multiple myeloma. Adoptive transfer of chimeric antigen receptor (CAR)-expressing T cells is a promising new therapy for hematologic malignancies, but an ideal target antigen for CAR-expressing T-cell therapies for multiple myeloma has not been identified. B-cell maturation antigen (BCMA) is a protein that has been reported to be selectively expressed by B-lineage cells including multiple myeloma cells...
April 15, 2013: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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