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

Frontiers in Immunology
Hannah M KnochelmannChrystal M Paulos

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.

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Methods Mentioned

BETA
glycosylation
transgenic

Clinical Trials Mentioned

NCT03089203
NCT02937844
NCT02930967
NCT00730613
NCT02992210
NCT02414269
NCT01822652
NCT03185468
NCT03179007
NCT03182803

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