Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction.
Vaccination with synthetic peptides representing cytotoxic T lymphocyte (CTL) epitopes can lead to a protective CTL-mediated immunity against tumors or viruses. We now report that vaccination with a CTL epitope derived from the human adenovirus type 5 E1A-region (Ad5E1A234-243), which can serve as a target for tumor-eradicating CTL, enhances rather than inhibits the growth of Ad5E1A-expressing tumors. This adverse effect of peptide vaccination was rapidly evoked, required low doses of peptide (10 micrograms), and was achieved by a mode of peptide delivery that induces protective T-cell-mediated immunity in other models. Ad5E1A-specific CTL activity could no longer be isolated from mice after injection of Ad5E1A-peptide, indicating that tolerization of Ad5E1A-specific CTL activity causes the enhanced tumor outgrowth. In contrast to peptide vaccination, immunization with adenovirus, expressing Ad5E1A, induced Ad5E1A-specific immunity and prevented the outgrowth of Ad5E1A-expressing tumors. These results show that immunization with synthetic peptides can lead to the elimination of anti-tumor CTL responses. These findings are important for the design of safe peptide-based vaccines against tumors, allogeneic organ transplants, and T-cell-mediated autoimmune diseases.
Toes
R E
RE
Department of Immunohematology and Blood Bank, University Hospital, Leiden, The Netherlands.
Offringa
R
R
Blom
R J
RJ
Melief
C J
CJ
Kast
W M
WM
D017500:Adenovirus E1A Proteins / Q000276:immunology*; D000260:Adenoviruses, Human; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D000939:Epitopes / Q000276:immunology; D011905:Genes, ras; D006801:Humans; D007111:Immunity, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology*; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
D017500:Adenovirus E1A Proteins; D000939:Epitopes; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014614:Vaccines, Synthetic; D014765:Viral Vaccines