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.
精准免疫肿瘤学通过识别并靶向肿瘤特异性抗原，以增强抗肿瘤免疫并改善实体瘤的治疗效果。胃癌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，已提高了不可切除或转移性胃癌患者的生存率。然而，肿瘤内分子异质性、分子靶标表达的可变性以及靶标表达的缺失，限制了抗体的使用及疗效的持久性。胃癌腹膜转移通常具有免疫学上的“冷肿瘤”特性，且弥漫性扩散至整个腹膜，对当前全身治疗策略构成尤为严峻的挑战。更具适应性的免疫治疗方法，如溶瘤病毒和嵌合抗原受体T细胞疗法，已成为有前景的胃癌及胃癌腹膜转移治疗手段，能够规避这些挑战。本研究系统综述了CAR-T细胞疗法针对关键原发性抗原靶点的临床前及临床疗效，并对用于治疗胃癌及胃癌腹膜转移的溶瘤病毒类型、修饰方式及作用机制进行了转化医学概述。最后，我们基于现有研究总结并探讨了溶瘤病毒与CAR-T细胞在治疗胃癌腹膜转移中潜在的协同作用机制。
肿瘤(癌症)患者之家