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

oleh: Hannah M. Knochelmann, Hannah M. Knochelmann, Aubrey S. Smith, Aubrey S. Smith, Connor J. Dwyer, Connor J. Dwyer, Megan M. Wyatt, Megan M. Wyatt, Shikhar Mehrotra, Shikhar Mehrotra, Chrystal M. Paulos, Chrystal M. Paulos

Format: Article
Diterbitkan: Frontiers Media S.A. 2018-07-01

Deskripsi

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.