Heat shock protein 70-peptide complex (HSP70-PC) (HSP70-PC)

The Heat shock protein 70-peptide complex (HSP70-PC) is a functional immunological unit consisting of the HSP70 chaperone protein bound to a repertoire of intracellularly derived peptides. In the context of immune activation, HSP70-PCs act as a bridge between the innate and adaptive immune systems by delivering antigenic cargo to professional antigen-presenting cells (APCs), such as dendritic cells. This process is mediated by specific receptors like CD91 (LRP1) and LOX-1, which facilitate the endocytosis of the complex and the subsequent cross-presentation of the chaperoned peptides on MHC Class I molecules to CD8+ cytotoxic T lymphocytes (CTLs). Beyond its role as a peptide carrier, HSP70 also functions as a potent adjuvant or danger signal that promotes dendritic cell maturation through the TLR4/NF-κB signaling pathway. Therapeutically, HSP70-PCs have been developed as autologous cancer vaccines, such as AG-858, where complexes are purified from a patient's own tumor to elicit a specific anti-tumor immune response. Additionally, specific peptides derived from the HSP70 protein itself can serve as epitopes for MHC I presentation, either to stimulate anti-tumor immunity or, in the case of autoimmune diseases like rheumatoid arthritis, to induce regulatory T cells (Tregs) and restore tolerance. Despite promising results in early-phase clinical trials for various malignancies, challenges remain regarding the immunogenicity and scalability of these personalized therapies.

Other names

HSP70-peptide complexHSP70-PCHSPPC-70Heat shock protein 70-chaperoned peptide complexChaperone-antigen complexHSP70-derived peptide-MHC complexHeat shock protein 70-mediated immune activation pathway