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表达 ICOS 的 CAR-T 细胞介导三阴性乳腺癌及转移的持久清除

英文原题:ICOS-expressing CAR-T cells mediate durable eradication of triple-negative breast cancer and metastasis.

查看英文原题

ICOS-expressing CAR-T cells mediate durable eradication of triple-negative breast cancer and metastasis.

PubMed 2025/03/18(内容时间) J Immunother Cancer Q1 · IF 11.7(JCR 2025)

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中文摘要

三阴性乳腺癌(TNBC)仍是侵袭性最强、治疗挑战最大的乳腺癌亚型之一。在近期研究中,Cao 等人开发了一种特异性靶向 B7H3、并持续表达诱导型共刺激分子(ICOS)的嵌合抗原受体(CAR)T 细胞(ICOS-B7H3-CAR-T);该疗法在临床前模型中清除了 TNBC,包括转移灶。这些 CAR-T 细胞利用 TNBC 细胞上的 ICOS 配体,通过 ICOS 信号增强抗肿瘤细胞毒作用。与传统 B7H3-CAR-T 细胞相比,ICOS-B7H3-CAR-T 细胞在小鼠异种移植模型中抗肿瘤疗效更强、细胞因子分泌增加且生存期延长。

该研究提示 ICOS 是改善 CAR-T 治疗实体瘤的有前景共刺激分子,并强调 ICOS 信号对增强治疗结局具有关键作用。本文讨论这些发现对 TNBC 治疗的意义、理解并利用 ICOS 生物学特征在免疫治疗中的重要性,以及优化 ICOS CAR-T 治疗实体瘤的未来方向。

展开英文摘要原文

Triple-negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging breast cancer subtypes. In their recent study, Cao et al introduced a B7H3-specific chimeric antigen receptor (CAR)-T cell with constitutive inducible co-stimulator (ICOS) expression (ICOS-B7H3-CAR-T), which demonstrated eradication of TNBC, including metastases, in preclinical models.

These CAR-T cells exploit the expression of ICOS ligand on TNBC cells, enhancing antitumor cytotoxicity through ICOS signaling. Compared with conventional B7H3-CAR-T cells, the ICOS-B7H3-CAR-T cells exhibited superior antitumor efficacy, increased cytokine secretion, and prolonged survival in xenograft murine models.

This study highlights ICOS as a promising co-stimulatory molecule for improving CAR-T therapy against solid tumors and underscores the critical role of ICOS signaling in enhancing therapeutic outcomes.

Here, we discuss the implications of these findings for TNBC treatment, the importance of understanding and exploiting ICOS biology in immunotherapies, and future directions for optimizing ICOS CAR-T cell therapies in solid tumor immunotherapy.

论文信息

作者
Herbrich S、Chaib M、Sharma P
第一作者单位
Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.United States
通讯作者单位
Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA padsharma@mdanderson.org.United States
期刊
Journal for immunotherapy of cancer2025 Mar 18
原文标识
PubMed 40107673 · DOI 10.1136/jitc-2025-011564