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探索妇科恶性肿瘤中的 T 细胞双特异性抗体

英文原题:Exploring T-cell bispecific antibodies in gynecologic malignancy.

查看英文原题

Exploring T-cell bispecific antibodies in gynecologic malignancy.

PubMed 2025/05/24(内容时间) Gynecol Oncol Rep Q3 · IF 1.5(JCR 2025)

研究概要

妇科癌症对女性健康构成重大挑战,由于传统治疗后复发率高,需要创新的治疗策略。

中文摘要

妇科癌症对女性健康构成重大挑战,尽管采用常规治疗,复发率仍然很高,因此需要创新的治疗策略。免疫治疗,特别是T细胞双特异性抗体(TCBs),通过重定向免疫系统靶向并消灭肿瘤细胞,提供了一种有前景的方法。TCBs同时结合肿瘤相关抗原和T细胞,诱导T细胞活化和肿瘤细胞裂解。虽然CAR T细胞疗法在血液系统恶性肿瘤中已显示出成功,但TCBs具有优势,例如作为“现货型”产品且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,重点关注其作用机制、临床前和临床数据以及安全性特征,同时探讨了挑战和未来方向。临床前数据突出显示了靶向AXL、MUC1、LYPD1和MUC16的TCBs在卵巢癌中展现出强效抗肿瘤活性。评估靶向MUC16的TCBs在卵巢癌和子宫内膜癌中的临床试验正在进行中。TCBs的安全性特征包括细胞因子释放综合征和靶向非肿瘤毒性等风险,需要谨慎管理。TCBs代表了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。

展开英文摘要原文

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.

论文信息

作者
O'Brien E、Mayer CM、Arend RC
单位
Department of Gynecologic Oncology, University of Alabama at Birmingham School of Medicine and O'Neal Comprehensive Cancer Center, Birmingham, AL, United States of America.United Kingdom
文献类型
综述
期刊
Gynecologic oncology reports2025 Jun
原文标识
PubMed 40502816 · DOI 10.1016/j.gore.2025.101772