Park Miso, Kim Ji Won
College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do Republic of Korea.
Jeju Research Institute of Pharmaceutical Sciences, College of Pharmacy, Jeju National University, Jeju-do, Republic of Korea.
Toxicol Res. 2024 Apr 22;40(3):335-348. doi: 10.1007/s43188-024-00233-4. eCollection 2024 Jul.
Monoclonal antibody (mAb)-based immunotherapy currently is considered to be an optimal therapeutic approach to cancer treatment, either in combination with surgery, radiation, and/or chemotherapy or alone. Various solid tumors and hematological malignancies have been characterized by distinct molecular targets, which could be utilized as innovative anticancer agents. Notably, receptor tyrosine kinases, including HER2, EGFR, VEGFR, and PDGFR, which act as receptors for growth factors, serve as crucial target proteins, expanding their role in the cancer therapeutic market. In contrast to conventional anticancer agents that directly target cancer cells, the advent of immunotherapy introduces novel approaches, such as immune checkpoint blockers (ICBs) and mAbs targeting surface antigens on immune cells in hematological malignancies and lymphomas. While these immunotherapies have mitigated the acquired resistance observed in traditional targeted therapies, they also exhibit diverse toxicities. Herein, this review focuses on describing the well-established toxicities and newly proposed mechanisms of monoclonal antibody toxicity in recent studies. Understanding these molecular mechanisms is indispensable to overcoming the limitations of mAbs-based therapies, facilitating the development of innovative anticancer agents, and uncovering novel indications for cancer treatment in the future.
基于单克隆抗体（mAb）的免疫疗法目前被认为是癌症治疗的一种最佳方法，无论是与手术、放疗和/或化疗联合使用还是单独使用。各种实体瘤和血液系统恶性肿瘤都具有独特的分子靶点，这些靶点可被用作创新的抗癌药物。值得注意的是，作为生长因子受体的受体酪氨酸激酶，包括HER2、EGFR、VEGFR和PDGFR，是关键的靶蛋白，这扩大了它们在癌症治疗市场中的作用。与直接靶向癌细胞的传统抗癌药物不同，免疫疗法的出现引入了新的方法，如免疫检查点阻断剂（ICB）以及针对血液系统恶性肿瘤和淋巴瘤中免疫细胞表面抗原的单克隆抗体。虽然这些免疫疗法减轻了传统靶向疗法中出现的获得性耐药性，但它们也表现出多种毒性。在此，本综述着重描述了近期研究中已明确的毒性以及新提出的单克隆抗体毒性机制。了解这些分子机制对于克服基于单克隆抗体疗法的局限性、推动创新抗癌药物的研发以及未来发现癌症治疗的新适应症而言不可或缺。
