Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors

• Published in: Science translational medicine Vol. 12; no. 559
• Main Authors: Park, Anthony K, Fong, Yuman, Kim, Sang-In, Yang, Jason, Murad, John P, Lu, Jianming, Jeang, Brook, Chang, Wen-Chung, Chen, Nanhai G, Thomas, Sandra H, Forman, Stephen J, Priceman, Saul J
• Format: Journal Article
• Language: English
• Published: United States 02.09.2020
• Subjects: Animals; Antigens, CD19; Immunotherapy; Immunotherapy, Adoptive; Mice; Neoplasms - therapy; Oncolytic Viruses; Receptors, Antigen, T-Cell
• ISSN: 1946-6242
• DOI: 10.1126/SCITRANSLMED.AAZ1863

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.