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CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies.


ABSTRACT: Genetic redirection of T lymphocytes with chimeric antigen receptors (CARs) has soared from treating cancers preclinically to FDA approval for hematologic malignancies and commercial-grade production scale in under 30?years. To date, solid tumors are less susceptible to CAR therapies and instead have been treated more successfully with immune checkpoint blockade or tumor-infiltrating lymphocyte therapy. Here, we discuss the current challenges in treating solid tumors with CAR T cells, and the obstacles within the host and tumor microenvironment hindering their efficacy. We present a novel three-pronged approach for enhancing the efficacy of CAR T cells whereby a single infusion product can synergize the power of an optimal CAR construct, a highly potent T cell subset, and rejuvenate the endogenous immune response to conquer therapeutically-resistant solid tumors.

SUBMITTER: Knochelmann HM 

PROVIDER: S-EPMC6094980 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies.

Knochelmann Hannah M HM   Smith Aubrey S AS   Dwyer Connor J CJ   Wyatt Megan M MM   Mehrotra Shikhar S   Paulos Chrystal M CM  

Frontiers in immunology 20180727


Genetic redirection of T lymphocytes with chimeric antigen receptors (CARs) has soared from treating cancers preclinically to FDA approval for hematologic malignancies and commercial-grade production scale in under 30 years. To date, solid tumors are less susceptible to CAR therapies and instead have been treated more successfully with immune checkpoint blockade or tumor-infiltrating lymphocyte therapy. Here, we discuss the current challenges in treating solid tumors with CAR T cells, and the ob  ...[more]

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