Stress protein/peptide complexes derived from autologous tumor tissue as tumor vaccines.
Vaccination of inbred mice with tumor-derived stress proteins hsp70, hsp90, and gp96/grp94 elicits a protective immunity to the tumor from which the vaccine was purified. There is now comprehensive experimental evidence that the antigenicity of tumor-derived hsp70, hsp90, and gp96 preparations results from diverse arrays of endogenous peptide antigens complexed with these stress proteins. Vaccination with tumor-derived stress protein/peptide complexes leads to their uptake and processing by professional antigen-presenting cells and to presentation of associated tumor peptide antigens to cytotoxic T cells. This induces a tumor-specific cytotoxic T cell response. The attractiveness of the concept of using tumor-derived stress proteins as vaccines is derived from two observations: (i) tumor stress protein vaccines mirror the individual antigenicity of a tumor, which results from random mutations due to genetic instability; and (ii) stress proteins represent powerful adjuvants for the peptide antigens complexed to them.
Heike
M
M
I. Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität Mainz, Germany. mheike@mail.uni-mainz.de
Weinmann
A
A
Bethke
K
K
Galle
P R
PR
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D018832:Molecular Chaperones / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D006649:Histocompatibility Antigens; D018832:Molecular Chaperones; C052646:sarcoma glycoprotein gp96 rejection antigens; C029237:tumor-associated transplantation antigen