嵌合抗原受体 T 细胞疗法在三阴性乳腺癌中的应用:追捕无形的恶魔。

CAR-T cell therapy in triple-negative breast cancer: Hunting the invisible devil.

机构信息

Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Department of Production Platforms & Analytics, Human Health Therapeutics Research Centre, National Research Council Canada, Montreal, QC, Canada.

出版信息

Front Immunol. 2022 Nov 22;13:1018786. doi: 10.3389/fimmu.2022.1018786. eCollection 2022.

Abstract

Triple-negative breast cancer (TNBC) is known as the most intricate and hard-to-treat subtype of breast cancer. TNBC cells do not express the well-known estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expressed by other breast cancer subtypes. This phenomenon leaves no room for novel treatment approaches including endocrine and HER2-specific antibody therapies. To date, surgery, radiotherapy, and systemic chemotherapy remain the principal therapy options for TNBC treatment. However, in numerous cases, these approaches either result in minimal clinical benefit or are nonfunctional, resulting in disease recurrence and poor prognosis. Nowadays, chimeric antigen receptor T cell (CAR-T) therapy is becoming more established as an option for the treatment of various types of hematologic malignancies. CAR-Ts are genetically engineered T lymphocytes that employ the body's immune system mechanisms to selectively recognize cancer cells expressing tumor-associated antigens (TAAs) of interest and efficiently eliminate them. However, despite the clinical triumph of CAR-T therapy in hematologic neoplasms, CAR-T therapy of solid tumors, including TNBC, has been much more challenging. In this review, we will discuss the success of CAR-T therapy in hematological neoplasms and its caveats in solid tumors, and then we summarize the potential CAR-T targetable TAAs in TNBC studied in different investigational stages.

摘要

三阴性乳腺癌(TNBC)是一种最为复杂且难以治疗的乳腺癌亚型。TNBC 细胞不表达其他乳腺癌亚型所表达的众所周知的雌激素受体、孕激素受体和人表皮生长因子受体 2(HER2)。这种现象使得新型治疗方法(包括内分泌和 HER2 特异性抗体治疗)没有用武之地。迄今为止,手术、放疗和全身化疗仍然是 TNBC 治疗的主要选择。然而,在许多情况下,这些方法要么导致最小的临床获益,要么无效,导致疾病复发和预后不良。如今,嵌合抗原受体 T 细胞(CAR-T)疗法作为治疗各种血液恶性肿瘤的一种选择越来越成熟。CAR-T 是经过基因工程改造的 T 淋巴细胞,利用人体免疫系统的机制来选择性地识别表达感兴趣的肿瘤相关抗原(TAA)的癌细胞,并有效地将其清除。然而,尽管 CAR-T 疗法在血液肿瘤学中取得了临床成功,但 CAR-T 疗法治疗实体瘤,包括 TNBC,却面临着更多的挑战。在这篇综述中,我们将讨论 CAR-T 疗法在血液肿瘤学中的成功及其在实体瘤中的局限性,然后总结不同研究阶段中 TNBC 中研究的潜在可靶向 CAR-T 的 TAA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47c9/9722775/102928d0e2da/fimmu-13-1018786-g001.jpg

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