Heat shock protein 70-tumor neoantigen peptide complex (HSP70-neoantigen complex)

Heat shock protein 70 (HSP70) is a molecular chaperone that can form complexes with tumor neoantigens or tumor-associated antigens (TAAs). The human HSP70 family consists of 13 homologs with a common structure featuring a nucleotide-binding domain and a substrate-binding domain. When complexed with tumor antigens, HSP70 can facilitate their presentation to immune cells, particularly dendritic cells, which then present these antigens in the context of MHC Class I or Class II complexes[1]. This mechanism forms the basis for HSP70-based anti-cancer immunotherapy. Exogenous HSP70 can penetrate cancer cells and displace intracellular HSP70, causing it to be released extracellularly along with tumor antigens. This process enhances the recognition of cancer cells by immune effectors like NK cells and cytotoxic lymphocytes[1]. Additionally, HSP70 exposed on the exterior of cancer cell membranes makes these cells more accessible to immune attack, particularly by NK cells through CD94 receptors, leading to the release of Granzyme B that targets the tumor cell[1]. HSP70-neoantigen complexes have been developed into personalized cancer vaccines, where patient-specific synthetic cancer neo-epitopes are complexed with HSP70 to stimulate anti-tumor immune responses[4]. Clinical trials are currently investigating this approach for malignant solid tumors[4]. The proliferation and cytotoxicity of CD4+ T cells can be enhanced by HSP70-antigen complexes, especially when combined with interleukins like IL-2, IL-7, IL-12, or IL-15[2]. While HSP70 plays a protective role in normal cells, its upregulation in cancer cells can promote disease progression and treatment resistance. Interestingly, HSP70 can be released extracellularly from cancer cells but rarely from normal cells, making extracellular HSP70 a potential cancer biomarker and therapeutic target[2].

Other names

HSP70-peptide complexHSP70-TAA complex (Tumor-Associated Antigen)Neoantigen-HSP70 peptide complex

Facilitates tumor antigen presentation to dendritic cells Enhances recognition of cancer cells by cytotoxic lymphocytes and NK cells Activates both innate and adaptive immunity against tumors Promotes CD4+ T cell proliferation and cytotoxicity when combined with cytokines