Liszewski M Kathryn, Atkinson John P
J Clin Invest. 2025 May 1;135(9). doi: 10.1172/JCI188355.
Initially identified as a regulator of complement activation on host cells, the known roles of CD46 (membrane cofactor protein [MCP]) have expanded. We now know that this ancient molecule is expressed on almost all nucleated cells as a family of four predominant isoforms. It also is involved in human reproduction, modulation of T cell activation and immunoinflammatory effector functions, autophagy, and the newly identified intracellular complement system (complosome). CD46 is also known as a "pathogen" magnet, being a port of entry for at least seven bacteria and five viruses. Moreover, CD46 has recently emerged as a key player in cancer biology. Numerous studies provide evidence of the association among elevated CD46 expression, malignant transformation, and metastasizing potential. These features, along with its roles as pathogen receptor, have made CD46 a target for cancer therapeutics. Thus, modified viral vectors (such as strains of adenovirus and measles virus) targeting CD46 currently are being exploited against a wide range of cancers. Another oncologic treatment utilizes a CD46-targeting human mAb as an antibody-drug conjugate. Herein, we review CD46 and its "multiverse" of cancer interactions.
CD46（膜辅因子蛋白[MCP]）最初被鉴定为宿主细胞补体激活的调节因子，其已知作用现已扩展。我们现在知道，这个古老的分子以四种主要异构体的形式在几乎所有有核细胞上表达。它还参与人类生殖、T细胞激活的调节和免疫炎症效应功能、自噬以及新发现的细胞内补体系统（补体小体）。CD46也被称为“病原体”磁体，是至少七种细菌和五种病毒的进入端口。此外，CD46最近已成为癌症生物学中的关键角色。大量研究提供了CD46表达升高、恶性转化和转移潜能之间关联的证据。这些特性，连同其作为病原体受体的作用，使CD46成为癌症治疗的靶点。因此，目前正在利用靶向CD46的修饰病毒载体（如腺病毒和麻疹病毒株）来对抗多种癌症。另一种肿瘤治疗方法是利用靶向CD46的人单克隆抗体作为抗体药物偶联物。在此，我们综述CD46及其与癌症相互作用的“多元世界”。
