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嵌合抗原受体 T 细胞疗法在结直肠癌和浸润性乳腺癌中的最新临床观点和挑战。

Updated Clinical Perspectives and Challenges of Chimeric Antigen Receptor-T Cell Therapy in Colorectal Cancer and Invasive Breast Cancer.

机构信息

I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, 119991, Russia.

Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Chiyyedu, Anantapuramu, Andhra Pradesh, 515721, India.

出版信息

Arch Immunol Ther Exp (Warsz). 2023 Aug 11;71(1):19. doi: 10.1007/s00005-023-00684-x.

Abstract

In recent years, the incidence of colorectal cancer (CRC) and breast cancer (BC) has increased worldwide and caused a higher mortality rate due to the lack of selective anti-tumor therapies. Current chemotherapies and surgical interventions are significantly preferred modalities to treat CRC or BC in advanced stages but the prognosis for patients with advanced CRC and BC remains dismal. The immunotherapy technique of chimeric antigen receptor (CAR)-T cells has resulted in significant clinical outcomes when treating hematologic malignancies. The novel CAR-T therapy target antigens include GUCY2C, CLEC14A, CD26, TEM8/ANTXR1, PDPN, PTK7, PODXL, CD44, CD19, CD20, CD22, BCMA, GD2, Mesothelin, TAG-72, CEA, EGFR, B7H3, HER2, IL13Ra2, MUC1, EpCAM, PSMA, PSCA, NKG2D. The significant aim of this review is to explore the recently updated information pertinent to several novel targets of CAR-T for CRC, and BC. We vividly described the challenges of CAR-T therapies when treating CRC or BC. The immunosuppressive microenvironment of solid tumors, the shortage of tumor-specific antigens, and post-treatment side effects are the major hindrances to promoting the development of CAR-T cells. Several clinical trials related to CAR-T immunotherapy against CRC or BC have already been in progress. This review benefits academicians, clinicians, and clinical oncologists to explore more about the novel CAR-T targets and overcome the challenges during this therapy.

摘要

近年来,由于缺乏选择性抗肿瘤治疗方法,结直肠癌(CRC)和乳腺癌(BC)的发病率在全球范围内呈上升趋势,导致死亡率更高。目前,化疗和手术干预是治疗晚期 CRC 和 BC 的主要方法,但晚期 CRC 和 BC 患者的预后仍然不佳。嵌合抗原受体(CAR)-T 细胞的免疫疗法在治疗血液恶性肿瘤方面取得了显著的临床疗效。新型 CAR-T 治疗的靶抗原包括 GUCY2C、CLEC14A、CD26、TEM8/ANTXR1、PDPN、PTK7、PODXL、CD44、CD19、CD20、CD22、BCMA、GD2、间皮素、TAG-72、CEA、EGFR、B7H3、HER2、IL13Ra2、MUC1、EpCAM、PSMA、PSCA、NKG2D。本综述的主要目的是探讨最近更新的关于 CAR-T 治疗 CRC 和 BC 的几个新型靶标的信息。我们生动地描述了 CAR-T 疗法治疗 CRC 或 BC 时所面临的挑战。实体肿瘤的免疫抑制微环境、肿瘤特异性抗原的缺乏以及治疗后的副作用是阻碍 CAR-T 细胞发展的主要障碍。目前已有几项与针对 CRC 或 BC 的 CAR-T 免疫疗法相关的临床试验正在进行中。本综述有助于学者、临床医生和临床肿瘤学家探索更多关于新型 CAR-T 靶点的信息,并克服该疗法中的挑战。

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