Heat shock protein 90 beta family member 1 (HSP90B1) (HSP90B1)

Heat shock protein 90 beta family member 1 (HSP90B1), commonly referred to as gp96, is a molecular chaperone located within the lumen of the endoplasmic reticulum (UniProt P14625). It plays a pivotal role in the maturation of various proteins, including integrins and Toll-like receptors, and is uniquely capable of binding a diverse repertoire of tumor-derived peptides (PubMed: 10661401). In the context of cancer immunotherapy, gp96-peptide complexes are utilized as autologous vaccines to stimulate the immune system against a patient's specific tumor profile. These complexes interact with the CD91 (LRP1) receptor on dendritic cells, which facilitates the internalization and subsequent cross-presentation of the chaperoned peptides on MHC class I molecules (PubMed: 12191486). This process triggers a robust activation of cytotoxic T lymphocytes (CTLs) targeted specifically at tumor cells. Clinical applications have focused on using purified gp96-peptide complexes, such as vitespen, to treat malignancies like glioblastoma and renal cell carcinoma by leveraging the protein's dual role as an antigen carrier and an immunological adjuvant (PubMed: 18413641).

Other names

gp96EndoplasminGRP-94TRA1Tumor rejection antigen 1Glucose-regulated protein 94

gp96-peptide complexes bind to the CD91 (LRP1) receptor on dendritic cells, triggering receptor-mediated endocytosis and subsequent cross-presentation of tumor-derived peptides on MHC class I molecules to activate CD8+ T cells (PubMed: 12191486, PubMed: 10661401).