ENHANCED TUMOR OUTGROWTH AFTER PEPTIDE VACCINATION - FUNCTIONAL DELETION OF TUMOR-SPECIFIC CTL INDUCED BY PEPTIDE VACCINATION CAN LEAD TO THE INABILITY TO REJECT TUMORS

CTL can play an important role in the defense against tumors. Protecti ve CTL-mediated immunity can be established in animal tumor models aft er vaccination with synthetic peptides representing CTL epitopes. We n ow report that immunization with synthetic peptides can also lead to C TL tolerance associated with the inability to reject tumors. B6 tumor cells transformed by the human adenovirus early region 1 (Ad5E1) prese nt an Ad5E1A- and an Ad5E1B-encoded CTL epitope to the immune system. CTL clones directed against either of these epitopes are able to eradi cate established Ad5E1-induced tumors, showing that these CTL epitopes are targets of CTL that can mediate tumor regression. Here, we show t hat protective immunity against Ad5E1-expressing tumor cells can be es tablished by immunization with Ad5E1-transformed cells and with an ade novirus vector containing the Ad5E1 region. Protective immunity, in ei ther case, is associated with specific CTL memory. To test whether vac cination with synthetic peptides leads to protection against Ad5E1-exp ressing tumor cells, we vaccinated mice s.c. with a low dose of the Ad 5E1B peptide. This peptide was chosen because the CTL response against the Ad5E1B-encoded CTL epitope contributes most to the antitumor resp onse in B6 mice after vaccination with Ad5E1-transformed cells. Ad5E1B peptide-vaccinated mice were not protected against the outgrowth of A d5E1-expressing tumor cells, but instead were no longer able to reject a tumor inoculum that was rejected by nonvaccinated mice. Moreover, t he protection induced by tumor cell vaccination against Ad5E1B-express ing tumors was gone when the Ad5E1B-encoded CTL epitope was injected a few days before tumor challenge. This is associated with peptide-indu ced tolerance of Ad5E1B-specific CTL activity. These findings are rele vant for the design of therapeutic approaches against both malignancie s and T cell-mediated autoimmune diseases.