Triple-negative breast cancer (TNBC), a highly aggressive breast cancer subtype that lacks estrogen receptor, progesterone receptor, and HER2 expression, does not respond to traditional endocrine and anti–HER2-targeted therapies. Current treatment options for patients with TNBC include a combination of surgery, radiotherapy, and/or systemic chemotherapy. FDA-approved therapies that target DNA damage repair mechanisms in TNBC, such as PARP inhibitors, only provide marginal clinical benefit. The immunogenic nature of TNBC has prompted researchers to harness the body's natural immune system to treat this aggressive breast cancer. Clinical precedent has been recently established with the FDA approval of two TNBC immunotherapies, including an antibody–drug conjugate and an anti-programmed death-ligand 1 monoclonal antibody. Chimeric antigen receptor (CAR)-T cell therapy, a type of adoptive cell therapy that combines the antigen specificity of an antibody with the effector functions of a T cell, has emerged as a promising immunotherapeutic strategy to improve the survival rates of patients with TNBC. Unlike the remarkable clinical success of CAR-T cell therapies in hematologic cancers with Kymriah and Yescarta, the development of CAR-T cell therapies for solid tumors has been much slower and is associated with unique challenges, including a hostile tumor microenvironment. The aim of the present review is to discuss novel approaches and inherent challenges pertaining to CAR-T cell therapy for the treatment of TNBC.

中文翻译：

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用于治疗三阴性乳腺癌的新兴 CAR-T 细胞疗法

三阴性乳腺癌 (TNBC) 是一种高度侵袭性的乳腺癌亚型，缺乏雌激素受体、孕激素受体和 HER2 表达，对传统的内分泌和抗 HER2 靶向治疗没有反应。目前 TNBC 患者的治疗选择包括手术、放疗和/或全身化疗的组合。FDA 批准的针对 TNBC 中 DNA 损伤修复机制的疗法，如 PARP 抑制剂，只能提供边际临床益处。TNBC 的免疫原性促使研究人员利用人体的天然免疫系统来治疗这种侵袭性乳腺癌。最近，FDA 批准了两种 TNBC 免疫疗法的临床先例，包括抗体药物偶联物和抗程序性死亡配体 1 单克隆抗体。嵌合抗原受体 (CAR)-T 细胞疗法是一种将抗体的抗原特异性与 T 细胞的效应子功能相结合的过继细胞疗法，已成为一种有前途的免疫治疗策略，可提高 TNBC 患者的存活率. 与 Kymriah 和 Yescarta 在血液系统癌症中取得的 CAR-T 细胞疗法的显着临床成功不同，用于实体瘤的 CAR-T 细胞疗法的开发要慢得多，并且面临着独特的挑战，包括敌对的肿瘤微环境。本综述的目的是讨论与 CAR-T 细胞疗法治疗 TNBC 相关的新方法和固有挑战。已成为一种有前途的免疫治疗策略，可提高 TNBC 患者的存活率。与 Kymriah 和 Yescarta 在血液系统癌症中取得的 CAR-T 细胞疗法的显着临床成功不同，用于实体瘤的 CAR-T 细胞疗法的开发要慢得多，并且面临着独特的挑战，包括敌对的肿瘤微环境。本综述的目的是讨论与 CAR-T 细胞疗法治疗 TNBC 相关的新方法和固有挑战。已成为一种有前途的免疫治疗策略，可提高 TNBC 患者的存活率。与 Kymriah 和 Yescarta 在血液系统癌症中取得的 CAR-T 细胞疗法的显着临床成功不同，用于实体瘤的 CAR-T 细胞疗法的开发要慢得多，并且面临着独特的挑战，包括敌对的肿瘤微环境。本综述的目的是讨论与 CAR-T 细胞疗法治疗 TNBC 相关的新方法和固有挑战。包括敌对的肿瘤微环境。本综述的目的是讨论与 CAR-T 细胞疗法治疗 TNBC 相关的新方法和固有挑战。包括敌对的肿瘤微环境。本综述的目的是讨论与 CAR-T 细胞疗法治疗 TNBC 相关的新方法和固有挑战。