Heat shock 70 kDa protein-peptide complex (Hsp70-peptide complex)

The Heat shock 70 kDa protein (Hsp70) substrate-binding domain-peptide complex is a molecular assembly that plays a critical role in the endogenous processing and presentation of antigens. Hsp70 is a molecular chaperone that utilizes its substrate-binding domain (SBD) to capture a broad repertoire of intracellular peptides, including those derived from mutated or overexpressed tumor proteins. In therapeutic applications, these complexes are often purified from a patient's own tumor tissue to create autologous vaccines, such as vitespen. The primary biological function of this complex in an immunological context is to deliver tumor-specific antigens to professional antigen-presenting cells (APCs) like dendritic cells. Upon binding to the CD91 receptor on the APC surface, the complex is endocytosed, and the peptides are channeled into the MHC class I and II pathways. This process, known as cross-presentation, triggers a potent and specific cytotoxic T-cell response against the tumor cells from which the peptides originated. While this approach offers a personalized immunotherapy strategy, its clinical success has been varied, leading to ongoing research into optimizing peptide loading and combination therapies with checkpoint inhibitors.

Other names

Tumor-derived peptide-Hsp70 complexHsp70 substrate-binding domain-peptide complexHsp70-SBD-peptide complexVitespenOncophageHSPPC-96

The complex acts as an immunogen where the Hsp70 component binds to the CD91 receptor on antigen-presenting cells (APCs), facilitating the internalization and cross-presentation of the bound tumor-derived peptides on MHC class I and II molecules to activate a T-cell mediated anti-tumor immune response.