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用异体恒定自然杀伤 T 细胞(iNKT)克服程序性细胞死亡蛋白 1(PD-1)阻断的耐药性

英文原题:Overcoming resistance to programmed cell death protein 1 (PD-1) blockade with allogeneic invariant natural killer T-cells (iNKT).

PubMed 2024/01/29(内容时间) Oncogene Q1 · IF 9.1(JCR 2025)

研究概要

胃癌是全球第5大常见恶性肿瘤,转移性疾病患者中仅有36%生存超过5年。

中文摘要

胃癌是全球第5大常见恶性肿瘤,转移性疾病患者中仅有36%生存超过5年。尽管随着免疫检查点抑制剂的出现治疗有所改善,但大多数胃癌患者仍会出现与肿瘤耐药相关的疾病进展。新型免疫治疗策略,包括恒定自然杀伤(iNKT)细胞,正在临床开发中,代表了克服耐药的潜在治疗选择。AgenT-797是一种来源于健康供者的同种异体人类未修饰iNKT。肿瘤脂质抗原对iNKT细胞的激活可触发直接细胞毒性,并通过分泌细胞因子和IFNγ促进间接抗肿瘤免疫应答,如招募和激活T细胞、NK细胞和树突状细胞。我们描述了一例微卫星高度不稳定(MSI-H)晚期胃腺癌患者在接受标准化疗和抗PD-1治疗进展后,经agent-797治疗出现免疫调节并导致持久肿瘤缓解。

展开英文摘要原文

Gastric cancer is the 5 th most common malignancy worldwide with only 36% of patients with metastatic disease surviving beyond 5 years. Despite therapeutic improvements with the advent of immune checkpoint inhibitors, most patients with gastric cancer develop disease progression related to tumor resistance. Novel immunotherapeutic approaches, including invariant natural killer (iNKT) cells, are in clinical development and represent potential therapeutic options to overcome resistance. AgenT-797 is an allogeneic human unmodified iNKT derived from healthy donors. Activation of iNKT cells by tumor lipid antigens can trigger direct cytotoxicity and promote indirect anti-tumor immune responses such as recruitment and activation of T cells, NK cells, and dendritic cells through secretion of cytokines and IFNγ. We describe immune modulation leading to durable tumor response in a patient with microsatellite instability-high (MSI-H) advanced gastric adenocarcinoma treated with agent-797 after progression on standard chemotherapy and anti-PD-1 therapy.

论文信息

作者
Hadfield MJ、Safran H、Purbhoo MA、Grossman JE、Buell JS、Carneiro BA
第一作者单位
Legorreta Cancer Center at Brown University, Lifespan Cancer Institute, Providence, RI, USA.United States
通讯作者单位
Legorreta Cancer Center at Brown University, Lifespan Cancer Institute, Providence, RI, USA. benedito_carneiro@brown.edu.United States
期刊
Oncogene2024 Mar
原文标识
PubMed 38281989 · DOI 10.1038/s41388-024-02948-y