Journal
FRONTIERS IN IMMUNOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.01740
Keywords
chimeric antigen receptor; T cell; solid tumor; adoptive cell transfer; checkpoint
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Funding
- NIH [T32 GM08716, T32 AI132164-01, R01 CA175061]
- ACS-IRG [016623-004]
- MUSC Start-up funds [R21 CA198646, 5 PO1 CA154778-05]
- KL2 South Carolina Clinical & Translational Research [UL1 TR000062]
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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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