T Cells Bearing a Chimeric Antigen Receptor against Prostate-Specific Membrane Antigen Mediate Vascular Disruption and Result in Tumor Regression

摘要

Aberrant blood vessels enable lumor growth, provide a barrier to immune infiltration, and serve as a source of protu-morigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here, we describe the ability of chimeric antigen receptor (CAR)-bearing T cells to recognize human prostate-specific membrane antigen (hl'SMA) on endothelial targets in vitro as well as iv vivo. CAR T cells were generated using the anti-PSMA scFv, J591, and the intracellular signaling domains: CD3zea, CD28, and/or CD137/ 4-1BB. We found that all anti-hl'SMA CAR T cells recognized and eliminated PSMA~+ endothelial targets in vitro, regardless of the signaling domain.