title: Heat-shock proteins-based immunotherapy for advanced melanoma in the era of target therapies and immunomodulating agents.
abstract: BACKGROUND
  Heat-shock proteins (HSPs) are highly conserved, stress-induced proteins that function as chaperones, stabilizing proteins and delivering peptides. Tumor-derived HSP peptide complexes (HSPPCs) induced immunity against several malignancies in preclinical models, exhibiting activity across tumor types.
  
  
  METHODS
  HSPPC-based vaccination showed clinical activity in subsets of patients with different malignancies (e.g., gastric, colorectal, pancreatic, ovarian cancer, and glioblastoma). In Phase III clinical trials for advanced melanoma and renal cell carcinoma patients, HSPPC-based vaccine demonstrated an excellent safety profile, thus emerging as a flexible tumor- and patient-specific therapeutic approach.
  
  
  CONCLUSIONS
  Melanoma, renal clear cell carcinoma, and glioblastoma are among suitable targets for HSP-based treatment as demonstrated by immune responses and clinical activity observed in subsets of patients, mainly those with early stage of disease and limited tumor burden. In order to further improve clinical activity, combinations of HSPPC-based vaccines with mutation-driven therapies, antiangiogenic agents, or immunomodulating monoclonal antibodies should be tested in controlled clinical trials.
authors.affiliation: Istituto Europeo di Oncologia, Melanoma and Sarcoma Division , Via Ripamonti 435, 2014i Milano , Italy +39 02 57489459 ; +39 02 94379230 ; giulio.tosti@ieo.it.
authors.forename: Giulio
authors.initials: G
authors.lastname: Tosti
authors.forename: Emilia
authors.initials: E
authors.lastname: Cocorocchio
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pennacchioli
authors.forename: Pier Francesco
authors.initials: PF
authors.lastname: Ferrucci
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.forename: Chiara
authors.initials: C
authors.lastname: Martinoli
mesh_terms: D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D005909:Glioblastoma / Q000276:immunology / Q000628:therapy*; D006360:Heat-Shock Proteins / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008954:Models, Biological; D010455:Peptides / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D007155:Immunologic Factors; D010455:Peptides
keywords: heat-shock protein; immunotherapy; melanoma