CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment

Frontiers in Immunology
Marina Martinez, Edmund Moon

Abstract

Chimeric antigen receptor (CAR) T cells, T cells that have been genetically engineered to express a receptor that recognizes a specific antigen, have given rise to breakthroughs in treating hematological malignancies. However, their success in treating solid tumors has been limited. The unique challenges posed to CAR T cell therapy by solid tumors can be described in three steps: finding, entering, and surviving in the tumor. The use of dual CAR designs that recognize multiple antigens at once and local administration of CAR T cells are both strategies that have been used to overcome the hurdle of localization to the tumor. Additionally, the immunosuppressive tumor microenvironment has implications for T cell function in terms of differentiation and exhaustion, and combining CARs with checkpoint blockade or depletion of other suppressive factors in the microenvironment has shown very promising results to mitigate the phenomenon of T cell exhaustion. Finally, identifying and overcoming mechanisms associated with dysfunction in CAR T cells is of vital importance to generating CAR T cells that can proliferate and successfully eliminate tumor cells. The structure and costimulatory domains chosen for the CAR may play an important ro...Continue Reading

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Methods Mentioned

BETA
xenograft
exome sequencing
transgenic
lymphodepletion
xenografts
gene knockouts

Clinical Trials Mentioned

NCT02959151
NCT02850536
NCT02349724
NCT03267173
NCT02541370
NCT03423992
NCT01837602
NCT03060356
NCT03672305
NCT03152435

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