title: Heated tumour cells of autologous and allogeneic origin elicit anti-tumour immunity.
abstract: Vaccination with established tumour cell lines may circumvent the problem of obtaining autologous tumour cells from patients, but may also need immunological adjuvants. Up-regulation of heat shock proteins within tumour cell vaccines has resulted in increased immunogenicity in some models, but this has yet to be demonstrated for allogeneic (MHC-disparate) cell vaccines. This was investigated here using a rat model for prostate tumour cell vaccination. Heating of tumour cells (42 degrees C, 1 h) elicited significant increases in HSP70 expression. Vaccination with heated autologous PAIII cells elicited protection against PAIII challenge in 60% of rats >50 days compared to 0% with unheated vaccine and was associated with an increased Th1 (IFNgamma) immune response. Heated allogeneic MLL cells elicited significant protection against PAIII challenge, in contrast to unheated cells. The principle was confirmed in two mouse models, although the allogeneic melanoma vaccine K1735 elicited the best protection when heated and administered mixed with autologous dendritic cells. Thus, while heating of vaccine cells in some models is highly beneficial, and is a means of enhancing immunogenicity without genetic modification or inclusion of potentially toxic adjuvants, additional immune enhancement may be required.
authors.affiliation: Division of Oncology, St. George's Hospital Medical School, Cranmer Terrace, London, SW17 0RE, UK. todryks@tcd.ie
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Todryk
authors.forename: Jonathan
authors.initials: J
authors.lastname: Eaton
authors.forename: Lindsay
authors.initials: L
authors.lastname: Birchall
authors.forename: Rebecca
authors.initials: R
authors.lastname: Greenhalgh
authors.forename: Diane
authors.initials: D
authors.lastname: Soars
authors.forename: Angus G
authors.initials: AG
authors.lastname: Dalgleish
authors.forename: Alan A
authors.initials: AA
authors.lastname: Melcher
authors.forename: Hardev S
authors.initials: HS
authors.lastname: Pandha
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000517:prevention & control; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006358:Hot Temperature; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000517:prevention & control; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D007371:Interferon-gamma