浅谈癌症免疫治疗中的新型免疫细胞接合器

A Discussion on New Immune Cell Adapters in Cancer Immunotherapy

免疫疗法是治疗癌症的一种革命性方法,包括基于细胞的疗法、疫苗、检查点抑制剂和靶向抗体,以及涉及免疫细胞接合器的最新方法。免疫细胞接合器是一种基于生物工程抗体的分子,旨在将免疫细胞重定向至肿瘤。大多数免疫细胞接合器是具有多个臂的抗体,通过靶向肿瘤抗原和效应细胞表面分子来桥接肿瘤细胞和效应细胞。效应细胞分子必须触发激活免疫效应细胞杀伤机制的信号通路。因此,这些分子的作用模式是在肿瘤细胞和免疫细胞之间形成免疫突触。第一代双特异性免疫细胞接合器被设计成靶向T细胞上CD3和白血病B细胞上的肿瘤抗原如CD19。这些药物在治疗血液系统恶性肿瘤患者方面已显示出良好的疗效,但仍存在许多挑战。特别是,细胞因子释放综合征(CRS)和免疫效应细胞相关的神经毒性,以及治疗后复发和实体瘤疗效不佳,都是严重的挑战。目前,人们正在努力提高T细胞接合器的安全性和有效性,包括开发对CD3具有较低亲和力的分子,靶向共刺激T细胞分子,并且可以在肿瘤微环境中被条件激活。此外,还正在探索靶向具有内在肿瘤细胞杀伤能力的其他类型的免疫效应细胞,如γδT细胞、自然杀伤(NK)细胞和髓系细胞。

Immunotherapy is a revolutionary approach to treating cancer,including cell-based therapies,vaccines,checkpoint inhibitors,and targeted antibodies,as well as the latest methods involving immune cell adapters.Immune cell adapter is a molecule based on bioengi-neered antibodies designed to redirect immune cells to tumors.Most immune cell adapters are antibodies with multiple arms that bridge tumor cells and effector cells by targeting tumor antigens and effector cell surface molecules.Effective cell molecules must trigger signaling pathways that activate immune effector cell killing mechanisms.Therefore,the mode of action of these molecules is to form immune syn-apses between tumor cells and immune cells.The first generation of bispecific immune cell adapters were designed to target CD3 on T cells and tumor antigens such as CD19 on leukemia B cells.These drugs have shown good efficacy in treating patients with hematological malig-nancies,but there are still many challenges.Especially,cytokine release syndrome(CRS)and immune effector cell related neurotoxicity,as well as poor efficacy in treating recurrence and solid tumors,are serious challenges.Currently,efforts are being made to improve the safety and effectiveness of T cell adapters,including developing molecules with low affinity for CD3,targeting co stimulatory T cell molecules,and being conditionally activated in the tumor microenvironment.In addition,we are also exploring targeting other types of immune effector cells with intrinsic tumor cell killing ability,such asγδT cells,natural killer(NK)cells,and myeloid cells.