State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Cancer Lett. 2021 Apr 10;503:69-74. doi: 10.1016/j.canlet.2021.01.014. Epub 2021 Jan 19.
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。它为以前难治性血液恶性肿瘤患者带来了治愈的希望。然而,当将该策略转化为非血液恶性肿瘤时,来自多项临床研究的抗肿瘤活性似乎较为微弱或短暂。实体瘤疗效较差的原因至少部分归因于抗原异质性、CAR-T 细胞迁移不良和肿瘤免疫抑制环境。在这里,我们将回顾更新的策略,以应对 CAR-T 疗法在非血液恶性肿瘤中的治疗障碍。我们主要关注与溶瘤病毒 (OV) 的联合,OV 是 CAR-T 细胞的天生盟友。除了之前报道的 OV 武装策略外,我们还讨论了最近提出的 OV 作为 CAR-T 靶点的肿瘤标记概念,以及可能的改进。总的来说,OV 联合 CAR-T 的肿瘤标记策略将为实体瘤的异质性和免疫抑制微环境提供一种新颖而有前途的解决方案。