Rybchenko Vladislav S, Aliev Teimur K, Panina Anna A, Kirpichnikov Mikhail P, Dolgikh Dmitry A
Bioengineering Department, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Department of Chemistry, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia.
Pharmaceutics. 2023 Jan 19;15(2):336. doi: 10.3390/pharmaceutics15020336.
Anti-tumor properties of several cytokines have already been investigated in multiple experiments and clinical trials. However, those studies evidenced substantial toxicities, even at low cytokine doses, and the lack of tumor specificity. These factors significantly limit clinical applications. Due to their high specificity and affinity, tumor-specific monoclonal antibodies or their antigen-binding fragments are capable of delivering fused cytokines to tumors and, therefore, of decreasing the number and severity of side effects, as well as of enhancing the therapeutic index. The present review surveys the actual antibody-cytokine fusion protein (immunocytokine) formats, their targets, mechanisms of action, and anti-tumor and other biological effects. Special attention is paid to the formats designed to prevent the off-target cytokine-receptor interactions, potentially inducing side effects. Here, we describe preclinical and clinical data and the efficacy of the antibody-mediated cytokine delivery approach, either as a single therapy or in combination with other agents.
几种细胞因子的抗肿瘤特性已经在多项实验和临床试验中进行了研究。然而，这些研究表明，即使在低细胞因子剂量下也存在显著毒性，并且缺乏肿瘤特异性。这些因素严重限制了临床应用。由于其高特异性和亲和力，肿瘤特异性单克隆抗体或其抗原结合片段能够将融合细胞因子递送至肿瘤，因此能够减少副作用的数量和严重程度，并提高治疗指数。本综述调查了实际的抗体 - 细胞因子融合蛋白（免疫细胞因子）形式、其靶点、作用机制以及抗肿瘤和其他生物学效应。特别关注旨在防止可能诱导副作用的脱靶细胞因子 - 受体相互作用的形式。在此，我们描述了临床前和临床数据以及抗体介导的细胞因子递送方法作为单一疗法或与其他药物联合使用时的疗效。
