Endoplasmin (gp96) (HSP90B1)

Endoplasmin, also known as gp96 or HSP90B1, is a molecular chaperone of the HSP90 family primarily located in the endoplasmic reticulum (UniProt P14625). It is essential for the folding and maturation of various proteins, including integrins and Toll-like receptors (PubMed: 11591751). A key immunological function of gp96 is its ability to bind and chaperone antigenic peptides, which are then delivered to antigen-presenting cells (APCs) (PubMed: 18437633). This delivery is mediated by the CD91 receptor on dendritic cells, facilitating the cross-presentation of antigens to CD8+ T cells (PubMed: 11160694). In oncology, the gp96-Ig fusion protein is engineered to be secreted from tumor cells, carrying a broad array of tumor-specific antigens to stimulate a polyvalent immune response (PubMed: 23867911). This approach is utilized in therapeutic vaccines like HS-110 (Viagenpumatucel-L) for treating non-small cell lung cancer (ClinicalTrials.gov: NCT02143466). By bypassing the need to identify specific neoantigens, the gp96-Ig platform provides an off-the-shelf solution for personalized immunotherapy. Clinical studies have shown that this mechanism can enhance tumor-infiltrating lymphocyte activity and improve patient outcomes when combined with checkpoint inhibitors.

Other names

gp96Grp94Heat shock protein 90 kDa beta member 1Tumor rejection antigen 1TRA1gp96-Ig

The gp96-Ig fusion protein acts as a chaperone that delivers tumor-associated antigenic peptides to dendritic cells via the CD91 receptor, facilitating cross-presentation and the induction of a cytotoxic T-cell response (PubMed: 18437633).