[Research Articles] Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors

Chimeric antigen receptor (CAR)–engineered T cell therapy for solid tumors is limited by the lack of both tumor-restricted and homogeneously expressed tumor antigens. Therefore, we engineered an oncolytic virus to express a nonsignaling, truncated CD19 (CD19t) protein for tumor-selective delivery, enabling targeting by CD19-CAR T cells. Infecting tumor cells with an oncolytic vaccinia virus coding for CD19t (OV19t) produced de novo CD19 at the cell surface before virus-mediated tumor lysis. Cocultured CD19-CAR T cells secreted cytokines and exhibited potent cytolytic activity against infected tumors. Using several mouse tumor models, delivery of OV19t promoted tumor control after CD19-CAR T cell administration. OV19t induced local immunity characterized by tumor infiltration of endogenous and adoptively transferred T cells. CAR T cell–mediated tumor killing also induced release of virus from dying tumor cells, which propagated tumor expression of CD19t. Our study features a combination immunotherapy approach using oncolytic viruses to promote de novo CAR T cell targeting of solid tumors.

Source: Science Translational Medicine - September 1, 2020 Category: Biomedical Science Authors: Park, A. K., Fong, Y., Kim, S.-I., Yang, J., Murad, J. P., Lu, J., Jeang, B., Chang, W.-C., Chen, N. G., Thomas, S. H., Forman, S. J., Priceman, S. J. Tags: Research Articles Source Type: research