Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction.

DOI Web Site 6 Citations
  • R E Toes
    Department of Immunohematology and Blood Bank, University Hospital, Leiden, The Netherlands.
  • R Offringa
    Department of Immunohematology and Blood Bank, University Hospital, Leiden, The Netherlands.
  • R J Blom
    Department of Immunohematology and Blood Bank, University Hospital, Leiden, The Netherlands.
  • C J Melief
    Department of Immunohematology and Blood Bank, University Hospital, Leiden, The Netherlands.
  • W M Kast
    Department of Immunohematology and Blood Bank, University Hospital, Leiden, The Netherlands.

Description

<jats:p>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.</jats:p>

Journal

Citations (6)*help

See more

Details 詳細情報について

Report a problem

Back to top