Heat shock protein derived from a non-autologous tumour can be used as an anti-tumour vaccine.
Antigenic cross-reactivity between certain tumours has allowed the development of more widely applicable, major histocompatibility complex-disparate (allogeneic) whole-cell vaccines. This principle should also allow heat shock proteins (hsp) derived from certain tumours (and carrying cross-reactive antigens) to be used as vaccines to generate anti-tumour immunity in a range of cancer patients. Here, hsp70 derived from gp70-antigen+ B16 melanoma generated cytotoxic-T-lymphocyte-mediated immune protection in BALB/c mice against challenge with gp70-antigen+ CT26 colorectal tumour cells. Using ovalbumin as a model tumour antigen, it is shown that hsp70 enhances peptide re-presentation by dendritic cells via class I over equimolar whole ovalbumin antigen. However, while transfection of tumour cells with inducible hsp70 increases hsp yield from tumours, it does not enhance antigen recognition via purified hsp70 nor via whole cells or their lysate.
Casey
David G
DG
Tumour Immunology Group, Institute of Immunology, National University of Ireland, Maynooth, Ireland.
Lysaght
Joanne
J
James
Tharappel
T
Bateman
Andrew
A
Melcher
Alan A
AA
Todryk
Stephen M
SM
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D003429:Cross Reactions / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000276:immunology*; D009368:Neoplasm Transplantation; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination / Q000379:methods
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D009363:Neoplasm Proteins