Viral Delivery of CAR Targets to Solid Tumors Enables Effective Cell Therapy

oleh: Amin Aalipour, Fabrice Le Boeuf, Matthew Tang, Surya Murty, Federico Simonetta, Alexander X. Lozano, Travis M. Shaffer, John C. Bell, Sanjiv S. Gambhir

Format: Article
Diterbitkan: Elsevier 2020-06-01

Deskripsi

Chimeric antigen receptor (CAR) T cell therapy has had limited efficacy for solid tumors, largely due to a lack of selectively and highly expressed surface antigens. To avoid reliance on a tumor’s endogenous antigens, here we describe a method of tumor-selective delivery of surface antigens using an oncolytic virus to enable a generalizable CAR T cell therapy. Using CD19 as our proof of concept, we engineered a thymidine kinase-disrupted vaccinia virus to selectively deliver CD19 to malignant cells, and thus demonstrated potentiation of CD19 CAR T cell activity against two tumor types in vitro. In an immunocompetent model of B16 melanoma, this combination markedly delayed tumor growth and improved median survival compared with antigen-mismatched combinations. We also found that CD19 delivery could improve CAR T cell activity against tumor cells that express low levels of cognate antigen, suggesting a potential application in counteracting antigen-low escape. This approach highlights the potential of engineering tumors for effective adoptive cell therapy.