Human GPRC5D Virus-Like Particles

GPRC5D (G protein-coupled receptor class C, group 5, member D) is an orphan receptor in the G protein-coupled receptor (GPCR) family, characterized by seven transmembrane domains and an extracellular N-terminus. While its precise physiological role remains under investigation, GPRC5D has garnered significant attention in the oncology field due to its selective overexpression in multiple myeloma (MM) and other hematological malignancies. Unlike other GPCRs, GPRC5D lacks a defined endogenous ligand, making it an "orphan" receptor. However, its restricted expression in malignant plasma cells and extremely low abundance in normal tissues make it an attractive therapeutic target.

GPRC5D virus-like particles (VLPs) are non-infectious nanostructures designed to mimic the native conformation of the GPRC5D receptor while removing viral genetic material. These VLPs consist of self-assembled viral capsid proteins with the GPRC5D antigen incorporated onto their surface, preserving the receptor''s tertiary structure and immunogenic epitopes. This design enables robust immune recognition without the risks associated with live virus. GPRC5D VLPs serve as a versatile platform for vaccine development, antibody production, and diagnostic toolkits. In cancer immunotherapy, they can be used as preventive vaccines or therapeutic agents, eliciting high-titer, specific immune responses against GPRC5D-expressing tumors. Furthermore, their particulate nature enhances antigen uptake by dendritic cells, promoting robust T and B cell activation. Beyond oncology, GPRC5D VLPs are also valuable tools for structural studies, aiding the exploration of receptor-ligand interactions and aiding in targeted drug discovery.