溶瘤病毒
嵌合抗原受体
免疫疗法
抗原
CD19
癌症研究
生物
肿瘤抗原
T细胞
癌症免疫疗法
病毒
病毒学
免疫系统
免疫学
肿瘤细胞
作者
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
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2020-09-02
卷期号:12 (559)
被引量:146
标识
DOI:10.1126/scitranslmed.aaz1863
摘要
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.
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