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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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):2625-2635 April 24, 2014 ©2014 by American Society of Hematology

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;123:2625-2635 ©2014 by American Society of Hematology

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;123:2625-2635 ©2014 by American Society of Hematology