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双特异性抗体在恶性黑色素瘤中的进展

Bispecific Antibodies Progression in Malignant Melanoma.

作者信息

Tang Juan, Gong Youling, Ma Xuelei

机构信息

Department of Oncology, West China Hospital of Sichuan University, Chengdu, China.

出版信息

Front Pharmacol. 2022 Mar 23;13:837889. doi: 10.3389/fphar.2022.837889. eCollection 2022.

Abstract

The discovery of oncogenes and immune checkpoints has revolutionized the treatment of melanoma in the past 10 years. However, the current PD-L1 checkpoints lack specificity for tumors and target normal cells expressing PD-L1, thus reducing the efficacy on malignant melanoma and increasing the side effects. In addition, the treatment options for primary or secondary drug-resistant melanoma are limited. Bispecific antibodies bind tumor cells and immune cells by simultaneously targeting two antigens, enhancing the anti-tumor targeting effect and cytotoxicity and reducing drug-resistance in malignant melanoma, thus representing an emerging strategy to improve the clinical efficacy. This review focused on the treatment of malignant melanoma by bispecific antibodies and summarized the effective results of the experiments that have been conducted, also discussing the different aspects of these therapies. The role of the melanoma epitopes, immune cell activation, cell death and cytotoxicity induced by bispecific antibodies were evaluated in the clinical or preclinical stage, as these therapies appear to be the most suitable in the treatment of malignant melanoma.

摘要

在过去十年中,癌基因和免疫检查点的发现彻底改变了黑色素瘤的治疗方式。然而,目前的程序性死亡受体配体1(PD-L1)检查点对肿瘤缺乏特异性,会靶向表达PD-L1的正常细胞,从而降低了对恶性黑色素瘤的疗效,并增加了副作用。此外,原发性或继发性耐药黑色素瘤的治疗选择有限。双特异性抗体通过同时靶向两种抗原,将肿瘤细胞和免疫细胞结合起来,增强抗肿瘤靶向作用和细胞毒性,并降低恶性黑色素瘤的耐药性,因此代表了一种提高临床疗效的新兴策略。这篇综述聚焦于双特异性抗体治疗恶性黑色素瘤,并总结了已开展实验的有效结果,还讨论了这些疗法的不同方面。在临床或临床前阶段评估了黑色素瘤表位、免疫细胞激活、双特异性抗体诱导的细胞死亡和细胞毒性的作用,因为这些疗法似乎最适合治疗恶性黑色素瘤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e50/8984188/65f51e636cc0/fphar-13-837889-g001.jpg

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