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Antibody-modified T cells: CARs take the front seat for hematologic malignancies by Marcela V. Maus, Stephan A. Grupp, David L. Porter, and Carl H. June.

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Presentation on theme: "Antibody-modified T cells: CARs take the front seat for hematologic malignancies by Marcela V. Maus, Stephan A. Grupp, David L. Porter, and Carl H. June."— Presentation transcript:

1 Antibody-modified T cells: CARs take the front seat for hematologic malignancies
by Marcela V. Maus, Stephan A. Grupp, David L. Porter, and Carl H. June Blood Volume 123(17): April 24, 2014 ©2014 by American Society of Hematology

2 Therapeutic approaches to overcome immune tolerance to tumors.
Therapeutic approaches to overcome immune tolerance to tumors. Cytokines and vaccines can be used to augment natural T-cell responses to tumor. Antibodies targeting negative regulatory molecules such as programmed death 1 (PD-1) and cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4) can be infused to release the brakes on natural T cells responsive to tumor. Chemotherapy can reduce immune suppressive cells such as Tregs and myeloid-derived suppressor cells (MDSC) in addition to its direct effect on the tumor cells. Adoptive T-cell transfer strategies using clonally expanded cytotoxic T cells or T cells engineered to express TCRs or CARs are being tested. Marcela V. Maus et al. Blood 2014;123: ©2014 by American Society of Hematology

3 Chimeric antigen receptors.
Chimeric antigen receptors. CARs target surface antigens in an MHC-independent fashion and consist of an ectodomain, hinge domain, transmembrane domain, and endodomain. The initial trials tested first-generation CARs that have a single cytoplasmic domain. Current trials are testing second- and third-generation CARs that have combinations of signaling domains. Marcela V. Maus et al. Blood 2014;123: ©2014 by American Society of Hematology


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