Chen Courtney, Jung Audrey, Yang Annie, Monroy Isabel, Zhang Zhifang, Chaurasiya Shyambabu, Deshpande Supriya, Priceman Saul, Fong Yuman, Park Anthony K, Woo Yanghee
Department of Surgery, City of Hope, Duarte, CA 91010, USA.
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA.
Cancers (Basel). 2023 Nov 30;15(23):5661. doi: 10.3390/cancers15235661.
Precision immune oncology capitalizes on identifying and targeting tumor-specific antigens to enhance anti-tumor immunity and improve the treatment outcomes of solid tumors. Gastric cancer (GC) is a molecularly heterogeneous disease where monoclonal antibodies against human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), and programmed cell death 1 (PD-1) combined with systemic chemotherapy have improved survival in patients with unresectable or metastatic GC. However, intratumoral molecular heterogeneity, variable molecular target expression, and loss of target expression have limited antibody use and the durability of response. Often immunogenically "cold" and diffusely spread throughout the peritoneum, GC peritoneal carcinomatosis (PC) is a particularly challenging, treatment-refractory entity for current systemic strategies. More adaptable immunotherapeutic approaches, such as oncolytic viruses (OVs) and chimeric antigen receptor (CAR) T cells, have emerged as promising GC and GCPC treatments that circumvent these challenges. In this study, we provide an up-to-date review of the pre-clinical and clinical efficacy of CAR T cell therapy for key primary antigen targets and provide a translational overview of the types, modifications, and mechanisms for OVs used against GC and GCPC. Finally, we present a novel, summary-based discussion on the potential synergistic interplay between OVs and CAR T cells to treat GCPC.
精准免疫肿瘤学利用识别和靶向肿瘤特异性抗原来增强抗肿瘤免疫力，并改善实体瘤的治疗效果。胃癌（GC）是一种分子异质性疾病，针对人表皮生长因子受体2（HER2）、血管内皮生长因子（VEGF）和程序性细胞死亡蛋白1（PD-1）的单克隆抗体联合全身化疗可提高不可切除或转移性GC患者的生存率。然而，肿瘤内分子异质性、分子靶点表达可变以及靶点表达缺失限制了抗体的使用和反应的持久性。GC腹膜转移癌（PC）通常具有免疫原性“冷”的特点，且广泛扩散至整个腹膜，对于当前的全身治疗策略而言，它是一个特别具有挑战性且难治的实体。更具适应性的免疫治疗方法，如溶瘤病毒（OVs）和嵌合抗原受体（CAR）T细胞，已成为有前景的GC和GCPC治疗方法，可规避这些挑战。在本研究中，我们对CAR T细胞疗法针对关键原发性抗原靶点的临床前和临床疗效进行了最新综述，并对用于GC和GCPC的OVs的类型、修饰和作用机制进行了转化概述。最后，我们就OVs和CAR T细胞治疗GCPC的潜在协同相互作用进行了基于总结的新颖讨论。
