Membrane cofactor protein (CD46) (CD46)

CD46, also known as membrane cofactor protein (MCP), is a ubiquitously expressed type I transmembrane glycoprotein that serves as a critical regulator of the innate immune system [1, 2]. Its primary biological function is to act as a cofactor for the serine protease factor I, which cleaves and inactivates the complement components C3b and C4b, thereby protecting host cells from complement-mediated damage [1, 4, 13]. Beyond its role in complement regulation, CD46 is involved in T-cell activation and differentiation, sperm-egg fusion, and serves as a receptor for several human pathogens, including the measles virus and certain adenoviruses [1, 2, 16]. In oncology, CD46 is frequently overexpressed in various malignancies, such as multiple myeloma and prostate cancer, often due to genomic amplification of the 1q21 locus [2, 8, 10]. This overexpression makes it an attractive therapeutic target for antibody-drug conjugates (ADCs) like FOR46 (FG-3246) and oncolytic viral therapies, which exploit its internalizing properties to deliver cytotoxic payloads or viral agents directly into tumor cells [7, 9, 17]. However, its broad expression across most nucleated cells presents a challenge for therapeutic window optimization and safety [1, 10].

Other names

MCPAHUS2MIC10TLXTRA2.10Cluster of differentiation 46

Antibody-drug conjugate (ADC) mediated cytotoxicity via macropinocytosis and payload release [8, 9]; receptor-mediated viral entry for oncolytic therapies [7, 13]; complement system modulation [1, 3].