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CAR-T 细胞与溶瘤病毒疗法治疗胃癌及胃癌源性腹膜癌病:改善联合策略之路

英文原题:Chimeric Antigen Receptor-T Cell and Oncolytic Viral Therapies for Gastric Cancer and Peritoneal Carcinomatosis of Gastric Origin: Path to Improving Combination Strategies.

PubMed 2023/11/30(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

研究概要

精准免疫肿瘤学依靠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结局。

中文摘要

精准免疫肿瘤学通过识别并靶向肿瘤特异性抗原,增强抗肿瘤免疫并改善实体瘤治疗结局。胃癌(GC)具有分子异质性;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,已改善不可切除或转移性GC患者的生存。然而,肿瘤内分子异质性、分子靶点表达差异以及靶点表达丢失,限制了抗体的应用和应答持久性。胃癌腹膜癌病(GCPC)常呈免疫学“冷”状态并弥漫播散于腹膜,是当前全身治疗难以克服、治疗抵抗显著的疾病。溶瘤病毒(OV)和嵌合抗原受体(CAR)T细胞等更具适应性的免疫治疗方式已成为有前景的GC及GCPC治疗方法,可绕开上述挑战。本研究综述了CAR-T细胞疗法针对关键原发抗原靶点的临床前和临床疗效最新进展,并从转化角度概述了用于治疗GC及GCPC的OV种类、改造方式和作用机制。最后,我们基于综述提出OV与CAR-T细胞治疗GCPC可能产生协同作用的新观点。

展开英文摘要原文

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.

论文信息

作者
Chen C、Jung A、Yang A、Monroy I、Zhang Z、Chaurasiya S、Deshpande S、Priceman S
单位
Department of Surgery, City of Hope, Duarte, CA 91010, USA.United States
文献类型
综述
期刊
Cancers2023 Nov 30
原文标识
PubMed 38067366 · DOI 10.3390/cancers15235661