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化学抗原受体树突细胞为癌症免疫疗法提供单个瘤杀伤因子的向输送

Rong Duan¹, Philip Milton^1,2, Chutamath Sittplangkoon¹

¹Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY, 14642, USA.

Cancer immunology, immunotherapy : CII

|August 6, 2024

概括

提供TNFα的工程树突细胞 (DCs) 与IAP抗剂相结合,有效地向并诱导乳腺癌细胞的亡. 这种新型的采用细胞疗法在治疗固体瘤方面表现有前途,同时最大限度地减少细胞因子释放综合征副作用.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
细胞生物学细胞生物学

背景情况:

化学抗原受体 (CAR) -T细胞对血液癌症有效,但对固体瘤不有效,通常会导致细胞因子释放综合征.
瘤亡因子α (TNFα) 是瘤杀伤性,但增加了阻断亡的亡蛋白 (IAP) 的抑制剂.
用对抗剂降解IAP,使癌细胞产生TNFα诱导的亡.

研究的目的:

开发一种用于固体癌症的新型采用细胞疗法,使用传递TNFα的工程树突细胞 (DCs).
评估用于乳腺癌治疗的TNFα递送DCs和IAP抗剂的组合.

主要方法:

人类树突细胞 (DCs) 被设计为表达TNFα和一种针对Mucin1的抗体片段 (M-DCs^TNF).
单独M-DCs^TNF和IAP抗剂SM-164的疗效在试验室和体内模型中对Mucin1阳性乳腺癌细胞进行了测试.

主要成果:

在人类乳腺癌细胞上,Mucin1的表达很高.
M-DCs^TNF加上SM-164在MDA-MB-231乳腺癌细胞中协同诱导的亡,这种效应被TNF抗体阻止.
结合M-DCs^TNF和SM-164在小鼠中抑制了患者衍生的乳腺癌的生长,而单独的SM-164则没有.

结论:

通过工程采用细胞与IAP抗剂相结合的TNFα的向输送是一种治疗乳腺癌的新有效策略.
这种方法为固体瘤的CAR-T细胞提供了潜在的替代方案,由于有限的细胞因子产生,降低了严重副作用的风险,如细胞因子释放综合征.

关键词:

乳腺癌乳腺癌乳腺癌化学抗原受体 (CAR) 细胞疗法树突细胞 (DC) 是一种干细胞.IAP 抗剂的对手亡蛋白抑制剂 (IAP) 是一种抑制剂.菌素 (Mucin) 是一种菌素.患者衍生异种移植 (PDX) 模型瘤亡因子-α (TNF) 的使用

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