[HTML][HTML] CAR T cells in solid tumors: blueprints for building effective therapies

HM Knochelmann, AS Smith, CJ Dwyer… - Frontiers in …, 2018 - frontiersin.org
HM Knochelmann, AS Smith, CJ Dwyer, MM Wyatt, S Mehrotra, CM Paulos
Frontiers in immunology, 2018frontiersin.org
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 …
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.
Frontiers