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使用密码子优化建立针对司抗性相关瘤相关抗原,CLSPN特异性强大的TCR-T细胞

Kanta Hori^1,2, Shuhei Yamada^1,2, Kenji Murata¹

¹Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Human vaccines & immunotherapeutics

|November 14, 2024

概括

针对CLSPN的优化T细胞受体工程T (TCR-T) 细胞对抗抗西斯普拉丁抗性膀癌的疗效提高. 这些先进的TCR-T细胞为组合疗法提供了有前途的策略,改善了治疗结果.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
细胞疗法细胞疗法

背景情况:

膀癌需要有效的全身疗法,免疫疗法显示出希望.
西斯普拉丁 (CDDP) 化疗是标准的,但可以抑制T细胞,阻碍组合免疫疗法.
经T细胞受体工程的T细胞 (TCR-T) 是一种强大的采用性T细胞治疗方法.

研究的目的:

开发和评估针对CLSPN瘤相关抗原的TCR-T细胞,用于膀癌治疗.
为了比较原始 (Ori) 和子优化 (Opt) TCR-T细胞的疗效.
评估Opt TCR-T细胞与CDDP结合治疗的潜力.

主要方法:

对抗原性HLA-A*02:01/CLSPN_1254-1262的特异性TCR-T细胞的发展.
从特定的CTL克隆中克隆TCR,随后进行编码子优化 (Opt TCR).
对Ori TCR-T细胞和Opt TCR-T细胞进行了转导效率,表达,激发和细胞毒性方面的比较分析.

主要成果:

与Ori的TCR-T细胞相比,Opt的TCR-T细胞表现出更高的转导效率,TCR表达和慕度.
选择的TCR-T细胞对膀癌细胞的细胞毒性显著增加.
开发的TCR-T细胞专门向了CDDP耐药膀癌中过度表达的CLSPN抗原.

结论:

针对HLA-A*02:01/CLSPN_1254-1262的代优化的TCR-T细胞显示出增强的抗瘤活性.
在膀癌中,opt TCR-T细胞是与西斯普拉丁联合治疗的有希望的候选者.
这种方法可以克服CDDP的免疫抑制作用,提高治疗疗效.

关键词:

在CLSPN中使用.在TCR-T中使用.尿路细胞癌是什么意思耐药性抗性抗性抗性抗性免疫疗法免疫疗法

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