Wen Junxu, Cui Wenxing, Yin Xiaoyan, Chen Yu, Liu Ailing, Wang Qian, Meng Xiangjiao
Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China.
Cancer Biol Med. 2025 Apr 7;22(4):348-75. doi: 10.20892/j.issn.2095-3941.2024.0470.
As the leading cause of cancer-related deaths, lung cancer remains a noteworthy threat to human health. Although immunotherapies, such as immune checkpoint inhibitors (ICIs), have significantly increased the efficacy of lung cancer treatment, a significant percentage of patients are not sensitive to immunotherapies and patients who initially respond to treatment can quickly develop acquired drug resistance. Bispecific antibodies (bsAbs) bind two different antigens or epitopes simultaneously and have been shown to enhance antitumor efficacy with suitable safety profiles, thus attracting increasing attention as novel antitumor therapies. At present, in addition to the approved bsAb, amivantamab, three novel bsAbs (KN046, AK112, and SHR-1701) are being evaluated in phase 3 clinical trials and many bsAbs are being evaluated in phase 1/2 clinical trials for patients with non-small cell lung cancer (NSCLC). Herein we present the structure, classification, and mechanism of action underlying bsAbs in NSCLC and introduce related clinical trials. Finally, we discuss challenges, potential solutions, and future prospects in the context of cancer treatment with bsAbs.
作为癌症相关死亡的主要原因,肺癌仍然是对人类健康的一个重大威胁。尽管免疫疗法,如免疫检查点抑制剂(ICIs),显著提高了肺癌治疗的疗效,但仍有相当比例的患者对免疫疗法不敏感,且最初对治疗有反应的患者可能很快会产生获得性耐药。双特异性抗体(bsAbs)能同时结合两种不同的抗原或表位,并已显示出在具有合适安全性的情况下增强抗肿瘤疗效,因此作为新型抗肿瘤疗法受到越来越多的关注。目前,除了已获批的双特异性抗体——氨伏单抗外,三种新型双特异性抗体(KN046、AK112和SHR-1701)正在进行3期临床试验评估,许多双特异性抗体正在针对非小细胞肺癌(NSCLC)患者进行1/2期临床试验评估。在此,我们介绍非小细胞肺癌中双特异性抗体的结构、分类及作用机制,并介绍相关临床试验。最后,我们在双特异性抗体癌症治疗的背景下讨论挑战、潜在解决方案和未来前景。
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