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抗原诱导的IL-12增强了piggyBac工程HER2-CAR-T细胞对抗胃癌的作用

Jinping Zhang¹, Lichen Zhang², Jinli Wang³

¹Department of Hematology, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China; Yunnan Province Clinical Research Center for Hematological Diseases, 650032 Kunming, China.

International immunopharmacology

|March 5, 2026

概括

机械T细胞分泌介质素-12 (IL-12) 显示增强胃癌治疗. 抗原诱导系统通过调节IL-12分泌提供了耐火性胃癌的有希望的策略.

科学领域:

免疫治疗是一种免疫疗法.
在瘤学瘤学.
分子生物学分子生物学

背景情况:

胃癌 (GC) 往往呈现晚期,需要新的治疗方法.
化学抗原受体 (CAR) T细胞疗法面临来自免疫抑制瘤微环境 (TME) 的挑战.
介质蛋白-12 (IL-12) 可以增强T细胞免疫力,并重编程TME.

研究的目的:

设计和评估IL-12分泌CAR T细胞用于胃癌治疗.
为了比较构成性与抗原诱导性IL-12分泌策略.
评估IL-12对T细胞表型,功能和抗瘤疗效在体外和体内的影响.

主要方法:

通过使用piggyBac转位子等离子体,设计了单链复合人体IL-12 (rhIL-12) 融合蛋白.
构造的构成性 (PB-IL-12) 和抗原诱导性 (NFAT-IL-12) IL-12分泌系统.
与HER2特异性CAR一起转移IL-12构造到人类T细胞中,并评估了抗瘤功效.

主要成果:

构成性IL-12分泌减少了T细胞的增殖,但丰富了CD4+和中央记忆T细胞.
IL-12分泌均增强了瘤细胞的杀死,独立于抗原密度.
两种IL-12系统在体内增强了抗瘤活性,构成性分泌显示出更高的全身细胞因子水平.

结论:

IL-12分泌显著提高了HER2-CAR-T细胞对胃癌的疗效.
抗原诱导系统保留T细胞的增殖潜力,并提供受调节的IL-12输送.
这种设计的IL-12分泌CAR T细胞策略对耐火性胃癌具有前途.

关键词:

它具有抗瘤活性.细胞疗法是一种细胞疗法.胃癌胃癌是指胃癌.在HER2-CAR-T细胞中.互乐金-12是其中一种.在 piggyBac 转位器上

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Tumor Immunotherapy

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