Open AccessEffective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors
Author(s) -
Anthony K. Park,
Yuman Fong,
Sangin Kim,
Jason Yang,
John P. Murad,
Jianming Lü,
Brook Jeang,
Wen-Chung Chang,
Nanhai G. Chen,
Sandra H. Thomas,
Stephen J. Forman,
Saul J. Priceman
Publication year - 2020
Publication title -
science translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.819
H-Index - 216
eISSN - 1946-6242
pISSN - 1946-6234
DOI - 10.1126/scitranslmed.aaz1863
Subject(s) - oncolytic virus , chimeric antigen receptor , immunotherapy , cancer research , antigen , cd19 , cancer immunotherapy , biology , tumor antigen , t cell , virus , virology , immunology , immune system , tumor cells
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.