Generation of autoreactive CTL by tumour vaccines containing foreign T helper epitopes

The aim of this study was to evaluate the effect of including a foreign T helper cell epitope in vaccines designed for generation of CTL against self-antigens and for inhibition of tumour growth. Two different vaccine designs were composed, a minimal epitope vaccine and a modified full length self-antigen, both based on OVA containing either a colinearily synthesized or an inserted Th-epitope, respectively. These vaccines were used for immunization of tolerant OVA transgenic mice (RIP-OVA(low)) and non-tolerant C57BL/6 mice. First, it was shown that transgenic mice were tolerant to OVA in the CD4 compartment. Secondly, only the vaccines containing the foreign Th-epitope and not the wild-type constructs were able to induce self-reactive CTL in the transgenic mice. Thirdly, these self-reactive CTL induced by the Th-epitope modified constructs also inhibited tumour growth in the OVA transgenic mice. Overall, these results demonstrate that inclusion of a foreign Th-epitope circumvents the tolerance in this OVA transgenic strain. In addition, these results show the importance of including strong T-cell help in cancer vaccines.