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靶向乳腺癌中的细胞毒性 T 淋巴细胞抗原 4(CTLA-4)

英文原题:Targeting cytotoxic lymphocyte antigen 4 (CTLA-4) in breast cancer.

查看英文原题

Targeting cytotoxic lymphocyte antigen 4 (CTLA-4) in breast cancer.

PubMed 2024/07/02(内容时间) Eur J Med Res Q2 · IF 4.8(JCR 2025)

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中文摘要

乳腺癌(BC)死亡率高,是全球最常见的恶性肿瘤之一。最初,BC被认为不具有免疫原性,但随着在BC肿瘤微环境中发现TIL(肿瘤浸润淋巴细胞)(TILs)和调节性T细胞(Tregs),这一范式发生了转变。CTLA-4(细胞毒性T淋巴细胞相关蛋白4)免疫治疗已成为BC的一种治疗选择,但其存在局限性,包括抗肿瘤效果欠佳和毒性。研究表明,抗CTLA-4联合治疗,如Treg清除、癌症疫苗和调节肠道微生物组,显著比CTLA-4单克隆抗体(mAB)单药治疗更有效。目前正在开发第二代CTLA-4抗体,以减轻免疫相关不良事件(irAEs)并增强抗肿瘤疗效。本综述探讨了抗CTLA-4 mAB在BC中作为单药治疗及与其他治疗联合应用的情况,并阐述了正在进行的临床试验、新型CTLA-4治疗策略以及生物标志物在BC中的潜在应用价值。

展开英文摘要原文

Breast cancer (BC) has a high mortality rate and is one of the most common malignancies in the world. Initially, BC was considered non-immunogenic, but a paradigm shift occurred with the discovery of tumor-infiltrating lymphocytes (TILs) and regulatory T cells (Tregs) in the BC tumor microenvironment. CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4) immunotherapy has emerged as a treatment option for BC, but it has limitations, including suboptimal antitumor effects and toxicity.

Research has demonstrated that anti-CTLA-4 combination therapies, such as Treg depletion, cancer vaccines, and modulation of the gut microbiome, are significantly more effective than CTLA-4 monoclonal antibody (mAB) monotherapy. Second-generation CTLA-4 antibodies are currently being developed to mitigate immune-related adverse events (irAEs) and augment antitumor efficacy.

This review examines anti-CTLA-4 mAB in BC, both as monotherapy and in combination with other treatments, and sheds light on ongoing clinical trials, novel CTLA-4 therapeutic strategies, and potential utility of biomarkers in BC.

论文信息

作者
Jama M、Tabana Y、Barakat KH
第一作者单位
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.Canada
通讯作者单位
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada. kbarakat@ualberta.ca.Canada
文献类型
综述
期刊
European journal of medical research2024 Jul 2
原文标识
PubMed 38956700 · DOI 10.1186/s40001-024-01901-9