Front Immunol. 2018 Jul 27;9:1740. doi: 10.3389/fimmu.2018.01740. eCollection 2018.

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

Knochelmann HM^1,2, Smith AS^1,2, Dwyer CJ^1,2, Wyatt MM^1,2, Mehrotra S^1,3, Paulos CM^1,2.

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.