在胃肠道癌症中基于细胞的疗法:当前的景观和未来的方向
Izuma Nakayama1, Kohei Shitara1
1Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
概括
基于细胞的疗法对胃肠道 (GI) 癌症具有前景,向CLDN18.2.2.等分子. 虽然存在诸如CAR-T枯竭等挑战,但下一代疗法和其他细胞类型为改善结果提供了潜力.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 胃肠病学 胃肠病学
背景情况:
- 基于细胞的疗法已在血液性恶性瘤中建立,并且在黑色素瘤等固体瘤中表现有前途.
- 基于细胞治疗在胃肠道 (GI) 癌症中取得成功的证据正在出现.
- 由于其特定的表达,CLDN18.2是胃癌 (GC) 的有希望的标.
研究的目的:
- 审查肠道癌的基于细胞的治疗方法的现状和未来潜力.
- 突出开发针对肠道恶性瘤的向细胞疗法的挑战和机遇.
- 讨论下一代治疗方法和治疗胃肠道癌症的替代细胞类型.
主要方法:
- 对瘤学中基于细胞的疗法现有文献的审查,重点关注肠道癌症.
- 分析挑战,包括瘤微环境,目标异质性和毒性.
- 探索新兴的细胞疗法策略,如下一代CAR-T,巨细胞和NK细胞疗法.
主要成果:
- 针对CLDN18.2的化学抗原受体T细胞 (CAR-T) 疗法在GC患者中显示出初始瘤缩.
- 由于CAR-T的耗尽和分子异质性,持久的反应仍然很少发生.
- 针对性,非瘤毒性是针对针对组织相关抗原的疗法的一个问题.
结论:
- 下一代CAR正在开发中,以克服抵抗机制.
- 采用巨细胞和自然杀手 (NK) 细胞疗法提供了潜在的疗效和现成生产.
- 先进的新抗原预测和T细胞激活策略可以在肠道癌症中推进TIL和T细胞受体-T疗法,可能改变治疗环境.
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