Antitumor vaccination using a major histocompatibility complex (MHC) classI-restricted pseudopeptide with reduced peptide bond

Synthetic peptides have raised a considerable interest in the fields of vac cines and immunotherapy. The authors previously introduced modifications in to the peptide backbone of the H-2K(d) restricted epitope CW3. One of these pseudopeptides, C7, bound to K-d with an affinity identical to the parent peptide and was recognized by T cells specific for the parent peptide. The authors now show that this analog has an increased resistance to trypsin an d displays an extended half-life in serum. The authors further tested its i mmunogenicity both in vitro and in vivo and found that cytotoxic T lymphocy tes (CTL) induced against the peptide analog recognize the parent peptide. Moreover, analysis of T-cell receptor rearrangements by Immunoscope softwar e revealed that C7-induced CTL display the hallmarks of the response agains t the parental epitope CW3. Administration of the pseudopeptide into DBA/2 mice induces a protective immune response against a lethal challenge with t umor cells expressing the parent peptide. Therefore, modifications in the b ackbone of antigenic peptides can decrease protease susceptibility while pr eserving immunogenicity. Such peptide analogues may therefore prove useful for the development of new therapeutic tools aimed at eradicating pathogens or tumors.