Chimeric antigen receptor (CAR) T cell therapy is one of the most promising immunotherapies in the past decade. It brings hope for cure to patients with previously refractory hematological malignancies. However, when translating this strategy into non-hematologic malignancies, the antitumor activity from multiple clinical studies seemed to be subtle or transient. The less satisfying efficacy in solid tumors might at least due to antigen heterogeneity, suboptimal CAR-T cell trafficking and tumor immunosuppressive environment. Here, we will review the updating strategies to challenge the therapeutic impediments of CAR-T therapy in non-hematologic malignancies. We mainly focus on the combination with oncolytic viruses (OV), the born allies for CAR-T cells. In addition to previously reported OVs-arming strategy, we discuss recently proposed tumor-tagging concept by OVs as CAR-T targets, as well as the possible improvements. Overall, tumor-tagging strategy by OVs combination with CAR-T would be a novel and promising solution for the heterogeneity and immunosuppressive microenvironment of solid tumors.

嵌合抗原受体 (CAR) T 细胞疗法是过去十年中最有前途的免疫疗法之一。它为以前难治的血液系统恶性肿瘤患者带来了治愈的希望。然而，当将此策略转化为非血液系统恶性肿瘤时，多项临床研究的抗肿瘤活性似乎是微妙或短暂的。在实体瘤中不太令人满意的疗效至少可能是由于抗原异质性、次优的 CAR-T 细胞运输和肿瘤免疫抑制环境。在这里，我们将回顾更新策略，以挑战 CAR-T 疗法在非血液系统恶性肿瘤中的治疗障碍。我们主要关注与溶瘤病毒（OV）的结合，这是 CAR-T 细胞的天生盟友。除了之前报道的 OVs-arming 策略之外，我们讨论了 OVs 最近提出的肿瘤标记概念作为 CAR-T 目标，以及可能的改进。总体而言，OVs 与 CAR-T 相结合的肿瘤标记策略将是解决实体瘤异质性和免疫抑制微环境的一种新颖且有前景的解决方案。