Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 12, Issue 559, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aaz1863
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Funding
- City of Hope Comprehensive Cancer Center Developmental Cancer Therapeutics (DCT) Program Pilot Projects
- T.J. Martell Foundation Cancer Research Grant
- National Cancer Institute of the National Institutes of Health [P30CA033572]
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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-CART cells secreted cytokines and exhibited potent cytolytic activity against infected tumors. Using several mouse tumor models, delivery of OV19t promoted tumor control after CD19-CART cell administration. OV19t induced local immunity characterized by tumor infiltration of endogenous and adoptively transferred T cells. CART 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 CART cell targeting of solid tumors.
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