Patient-specific tumor neoantigen peptides complexed with Heat Shock Protein 70 (HSP70-PC)

Patient-specific tumor neoantigen peptides complexed with Heat Shock Protein 70 (HSP70) represent a personalized immunotherapy approach designed to elicit a robust anti-tumor immune response. HSP70, a highly conserved molecular chaperone, naturally binds to a diverse array of intracellular peptides, including those derived from tumor-specific mutations known as neoantigens. In this therapeutic strategy, these complexes are typically purified from a patient's own tumor tissue and administered as a vaccine. The HSP70 component serves a dual role: it acts as a delivery vehicle that targets specific receptors on antigen-presenting cells (APCs)—such as CD91, LOX-1, and scavenger receptors—and functions as an adjuvant (chaperokine) that stimulates dendritic cell maturation. Once internalized by APCs, the chaperoned neoantigens are cross-presented on MHC class I and II molecules, triggering the activation of both cytotoxic CD8+ T cells and helper CD4+ T cells specifically primed to recognize and destroy the patient's unique tumor cells. Clinical investigations have demonstrated that this approach is generally safe and can induce long-lasting immune memory, particularly when combined with immune checkpoint inhibitors.

Other names

HSP70-peptide complexHSP70-PCAutologous tumor-derived HSP70-peptide complexHSP70-neoantigen vaccineHSP70-chaperoned neoantigens

HSP70 acts as a chaperone for patient-specific tumor neoantigens, binding to receptors on antigen-presenting cells (APCs) such as CD91, LOX-1, SREC-1, and TLR2/4. This interaction facilitates the endocytosis and cross-presentation of the neoantigens on MHC class I and II molecules, leading to the activation of tumor-specific CD8+ and CD4+ T cells. Additionally, HSP70 acts as a chaperokine, inducing DC maturation and pro-inflammatory cytokine release via the NF-κB pathway.