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.

嵌合抗原受体 (CAR) 工程化 T 细胞治疗实体瘤受到缺乏肿瘤限制性和均质表达的肿瘤抗原的限制。因此，我们设计了一种溶瘤病毒来表达一种非信号转导、截短的 CD19 (CD19t) 蛋白，用于肿瘤选择性递送，从而能够被 CD19-CAR T 细胞靶向。在病毒介导的肿瘤溶解之前，用编码 CD19t (OV19t) 的溶瘤痘苗病毒感染肿瘤细胞在细胞表面产生新的 CD19。共培养的 CD19-CAR T 细胞分泌细胞因子并对感染的肿瘤表现出有效的细胞溶解活性。使用几种小鼠肿瘤模型，OV19t 的递送促进了 CD19-CAR T 细胞给药后的肿瘤控制。OV19t 诱导局部免疫，其特征在于内源性和过继转移的 T 细胞的肿瘤浸润。CAR T 细胞介导的肿瘤杀伤还诱导死亡肿瘤细胞释放病毒，从而促进 CD19t 的肿瘤表达。我们的研究采用联合免疫治疗方法，使用溶瘤病毒促进从头 CAR T 细胞靶向实体瘤。