Department of Breast Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
School of Medicine, Zhejiang University, Hangzhou, China.
Cancer. 2024 Apr 15;130(S8):1378-1391. doi: 10.1002/cncr.35096. Epub 2023 Nov 11.
Breast cancer (BC) is the fourth most prevalent cancer in China. Despite conventional treatment strategies, BC patients often have poor therapeutic outcomes, leading to significant global cancer mortality rates. Chimeric antigen receptor (CAR)-based immunotherapy is a promising and innovative approach for cancer treatment that redirects immune cells to attack tumor cells expressing selected tumor antigens (TAs). T cells, natural killer (NK) cells, and macrophages, key components of the immune system, are used in CAR-based immunotherapies. Although remarkable progress has been made with CAR-T cells in hematologic malignancies, the application of CAR-based immunotherapy to BC has lagged. This is partly due to obstacles such as tumor heterogeneity, which is further associated with the TA and BC subtypes, and the immunosuppressive tumor microenvironment (TME). Several combinatorial approaches, including the use of immune checkpoint inhibitors, oncolytic viruses, and antitumor drugs, have been proposed to overcome these obstacles in BC treatment. Furthermore, several CAR-based immunotherapies for BC have been translated into clinical trials. This review provides an overview of the recent progress in CAR-based immunotherapy for BC treatment, including targeting of TAs, consideration of BC subtypes, assessment of the TME, and exploration of combinatorial therapies. The authors focused on preclinical studies and clinical trials of CAR-T cells, CAR-NK cells, and CAR-macrophages especially conducted in China, followed by an internal comparison and discussion of current limits. In conclusion, this review elucidates China's contribution to CAR-based immunotherapies for BC and provides inspiration for further research. PLAIN LANGUAGE SUMMARY: Despite conventional treatment strategies, breast cancer (BC) patients in China often have poor therapeutic outcomes. Chimeric antigen receptor (CAR)-based immunotherapy, a promising approach, can redirect immune cells to kill tumor cells expressing selected tumor antigens (TAs). However, obstacles such as TA selection, BC subtypes, and immunosuppressive tumor microenvironment still exist. Therefore, various combinatorial approaches have been proposed. This article elucidates several Chinese CAR-based preclinical and clinical studies in BC treatment with comparisons of foreign research, and CAR-immune cells are analyzed, providing inspiration for further research.
在中国,乳腺癌(BC)是第四大常见癌症。尽管采用了常规治疗策略,但 BC 患者的治疗效果往往不佳,导致全球癌症死亡率居高不下。嵌合抗原受体(CAR)为基础的免疫疗法是一种有前途的创新癌症治疗方法,它可以使免疫细胞定向攻击表达选定肿瘤抗原(TA)的肿瘤细胞。CAR 为基础的免疫疗法中使用了 T 细胞、自然杀伤(NK)细胞和巨噬细胞等免疫系统的关键组成部分。尽管 CAR-T 细胞在血液恶性肿瘤方面取得了显著进展,但 CAR 为基础的免疫疗法在 BC 中的应用却落后了。这在一定程度上是由于肿瘤异质性等障碍造成的,肿瘤异质性与 TA 和 BC 亚型进一步相关,以及免疫抑制性肿瘤微环境(TME)。已经提出了几种组合方法,包括使用免疫检查点抑制剂、溶瘤病毒和抗肿瘤药物,以克服 BC 治疗中的这些障碍。此外,几种针对 BC 的 CAR 为基础的免疫疗法已转化为临床试验。本综述概述了 CAR 为基础的 BC 治疗免疫疗法的最新进展,包括针对 TA、考虑 BC 亚型、评估 TME 以及探索组合疗法。作者重点关注了在中国进行的 CAR-T 细胞、CAR-NK 细胞和 CAR-巨噬细胞的临床前研究和临床试验,随后进行了内部比较和讨论当前的局限性。总之,本综述阐明了中国在 CAR 为基础的 BC 免疫疗法方面的贡献,并为进一步的研究提供了启示。
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