title: High molecular weight stress proteins: Identification, cloning and utilisation in cancer immunotherapy.
abstract: Although the large stress/heat shock proteins (HSPs), i.e. Hsp110 and Grp170, were identified over 30 years ago, these abundant and highly conserved molecules have received much less attention compared to other conventional HSPs. Large stress proteins act as molecular chaperones with exceptional protein-holding capability and prevent the aggregation of proteins induced by thermal stress. The chaperoning properties of Hsp110 and Grp170 are integral to the ability of these molecules to modulate immune functions and are essential for developing large chaperone complex vaccines for cancer immunotherapy. The potent anti-tumour activity of the Hsp110/Grp170-tumour protein antigen complexes demonstrated in preclinical studies has led to a phase I clinical trial through the National Cancer Institute's rapid access to intervention development (RAID) programme that is presently underway. Here we review aspects of the structure and function of these large stress proteins, their roles as molecular chaperones in the biology of cell stress, and prospects for their use in immune regulation and cancer immunotherapy. Lastly, we will discuss the recently revealed immunosuppressive activity of scavenger receptor A that binds to Hsp110 and Grp170, as well as the feasibility of targeting this receptor to promote T-cell activation and anti-tumour immunity induced by large HSP vaccines and other immunotherapies.
authors.affiliation: Department of Human Molecular Genetics, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Wang
authors.forename: John R
authors.initials: JR
authors.lastname: Subjeck
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use; D050957:HSP110 Heat-Shock Proteins / Q000737:chemistry / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000502:physiology; D006801:Humans; D007167:Immunotherapy; D008970:Molecular Weight; D009369:Neoplasms / Q000628:therapy
chemical_list: D019496:Cancer Vaccines; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins