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探索双特异性T细胞抗体在妇科恶性肿瘤中的应用。

Exploring T-cell bispecific antibodies in gynecologic malignancy.

作者信息

O'Brien Emily, Mayer Christopher M, Arend Rebecca C

机构信息

Department of Gynecologic Oncology, University of Alabama at Birmingham School of Medicine and O'Neal Comprehensive Cancer Center, Birmingham, AL, United States of America.

出版信息

Gynecol Oncol Rep. 2025 May 24;59:101772. doi: 10.1016/j.gore.2025.101772. eCollection 2025 Jun.

Abstract

Gynecologic cancers present a significant challenge to women's health, necessitating innovative therapeutic strategies due to high relapse rates despite conventional treatments. Immunotherapy, particularly T-cell bispecific antibodies (TCBs), offers a promising approach by redirecting the immune system to target and eliminate tumor cells. TCBs bind simultaneously to tumor-associated antigens and T cells, inducing T-cell activation and tumor cell lysis. While CAR T-cell therapies have shown success in hematologic malignancies, TCBs offer advantages such as being "off-the-shelf" products with lower rates of severe toxicities. This review provides an overview of TCBs in gynecologic malignancies, focusing on their mechanisms of action, preclinical and clinical data, and safety profiles, while also addressing the challenges and future directions. Preclinical data highlight TCBs targeting AXL, MUC1, LYPD1, and MUC16 in ovarian cancer, demonstrating potent antitumor activity. Clinical trials evaluating MUC16-targeted TCBs in ovarian and endometrial cancers are ongoing. The safety profile of TCBs includes risks such as cytokine release syndrome and on-target off-tumor toxicity, which require careful management. TCBs represent a promising immunotherapeutic approach for gynecologic cancers, warranting further investigation to optimize their efficacy and safety.

摘要

妇科癌症对女性健康构成重大挑战,尽管采用了传统治疗方法,但由于复发率高,需要创新的治疗策略。免疫疗法,特别是T细胞双特异性抗体(TCBs),通过重新引导免疫系统靶向并消除肿瘤细胞,提供了一种有前景的方法。TCBs同时与肿瘤相关抗原和T细胞结合,诱导T细胞活化和肿瘤细胞裂解。虽然嵌合抗原受体(CAR)T细胞疗法在血液系统恶性肿瘤中已显示出成效,但TCBs具有一些优势,如为“现成可用”产品,严重毒性发生率较低。本综述概述了TCBs在妇科恶性肿瘤中的应用,重点介绍其作用机制、临床前和临床数据以及安全性概况,同时也探讨了面临的挑战和未来方向。临床前数据突出了针对卵巢癌中AXL、MUC1、LYPD1和MUC16的TCBs,显示出强大的抗肿瘤活性。评估针对卵巢癌和子宫内膜癌中MUC16的TCBs的临床试验正在进行中。TCBs的安全性概况包括细胞因子释放综合征和靶向非肿瘤毒性等风险,需要仔细管理。TCBs是一种有前景的妇科癌症免疫治疗方法,值得进一步研究以优化其疗效和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a74/12158561/32dbc78232cd/gr1.jpg

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