PEPTIDE VACCINATION CAN LEAD TO ENHANCED TUMOR-GROWTH THROUGH SPECIFIC T-CELL TOLERANCE INDUCTION

Vaccination with synthetic peptides representing cytotoxic T lymphocyt e (CTL) epitopes can lead to a protective CTL-mediated immunity agains t tumors or viruses. We now report that vaccination with a CTL epitope derived from the human adenovirus type 5 E1A-region (Ad5E1A(234-243)) , which can serve as a target for tumore-radicating CTL, enhances rath er than inhibits the growth of Ad5E1A-expressing tumors. This adverse effect of peptide vaccination was rapidly evoked, required low doses o f peptide (10 mu g), and was achieved by a mode of peptide delivery th at induces protective T-cell-mediated immunity in other models. Ad5E1A -specific CTL activity could no longer be isolated from mice after inj ection of Ad5E1A-peptide, indicating that tolerization of Ad5E1A-speci fic CTL activity causes the enhanced tumor outgrowth. In contrast to p eptide vaccination, immunization with adenovirus, expressing Ad5E1A, i nduced 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. The se findings are important for the design of safe peptide-based vaccine s against tumors, allogeneic organ transplants, and T-cell-mediated au toimmune diseases.