Antitumor vaccination using a major histocompatibility complex (MHC) class I-restricted pseudopeptide with reduced peptide bond.
Synthetic peptides have raised a considerable interest in the fields of vaccines and immunotherapy. The authors previously introduced modifications into the peptide backbone of the H-2Kd-restricted epitope CW3. One of these pseudopeptides, C7, bound to Kd 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 and displays an extended half-life in serum. The authors further tested its immunogenicity both in vitro and in vivo and found that cytotoxic T lymphocytes (CTL) induced against the peptide analog recognize the parent peptide. Moreover, analysis of T-cell receptor rearrangements by Immunoscope software revealed that C7-induced CTL display the hallmarks of the response against the parental epitope CW3. Administration of the pseudopeptide into DBA/2 mice induces a protective immune response against a lethal challenge with tumor cells expressing the parent peptide. Therefore, modifications in the backbone of antigenic peptides can decrease protease susceptibility while preserving immunogenicity. Such peptide analogues may therefore prove useful for the development of new therapeutic tools aimed at eradicating pathogens or tumors.
Calbo
S
S
Unité de Biologie Moléculaire du Gène, INSERM U277, Institut Pasteur, Paris, France.
Guichard
G
G
Muller
S
S
Kourilsky
P
P
Briand
J P
JP
Abastado
J P
JP
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D010455:Peptides / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014357:Trypsin / Q000378:metabolism; D014611:Vaccination
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014357:Trypsin