Chimeric antigen receptor T cells as adjuvant therapy for unresectable adenocarcinoma.

Abstract

Incomplete surgery of solid tumors is a risk factor for primary treatment failure. Here, we have investigated whether chimeric antigen receptor T cells (CARTs) could be used as an adjuvant therapy to clear residual cancer cells. We tested the feasibility of this approach in two partial resection xenograft models using mesothelin-specific CARTs. In addition, we developed a previously unexplored in vivo toxicity model to evaluate safety and effects on wound healing in immunocompetent C57BL/6 mice. We found that the local delivery of CARTs in a fibrin glue-based carrier was effective in clearing residual cancer cells following incomplete surgery. This resulted in significantly longer overall survival when compared to mice treated with surgery and CARTs without fibrin glue. On-target off-tumor toxicity was diminished, and wound healing complications were not seen in any of the mice. On the basis of these observations, a clinical trial in patients with locally advanced breast cancer is planned.