Nonmutated self-antigen-derived cancer vaccine peptides elicit an IgE-independent but mast cell-dependent immediate-type skin reaction without systemic anaphylaxis.
We previously reported an unexpected phenomenon, i.e., several cancer vaccine peptides, including a cyclophilin B-derived peptide (CypB-84), elicited an immediate-type skin reaction in prevaccination skin tests. These peptides were prohibited in the subsequent vaccinations because of a possible induction of systemic anaphylaxis. In this study, we investigated mechanisms involved in the peptide-elicited inflammatory reactions in BALB/c mice whose MHC class I molecule (Kd) shared similar binding motifs with the human HLA-A24 molecule. Among 11 peptides tested, all of which had been scheduled for use in clinical trials with HLA-A24+ cancer patients, three peptides (CypB-84, ART1-170, and ART4-13) elicited immediate footpad reactions in BALB/c mice similar to the skin reactions in humans. The footpad reaction was also observed in C57BL/6, athymic nu/nu, and CB17-SCID mice, but not in mast cell-deficient WBB6F1w/wv mice, indicating the reaction was not mediated by specific immunity, but was mast cell-dependent. Furthermore, the reactions were not correlated to in vivo antitumor effects of the peptides. An anaphylaxis was not elicited when the peptides were systemically injected due to a very rapid clearance of the peptides from the plasma by in vivo degradation. These results suggest that certain peptides of cancer vaccine candidates exhibit an IgE-independent but mast cell-dependent inflammatory response with no elicitation of systemic anaphylaxis, and may provide new insights for further development of peptide-based vaccinations for cancer patients.
Yamada
Akira
A
Cancer Vaccine Development Division, Research Center for Innovative Cancer Therapy, and Center of the 21st Century Center of Excellence Program for Medical Science, Kurume University, Kurume, Japan. akiymd@med.kurume-u.ac.jp
Yano
Hirohisa
H
Takao
Yukari
Y
Ono
Takeharu
T
Matsumoto
Tomoko
T
Itoh
Kyogo
K
D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D001324:Autoantigens / Q000235:genetics; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D016513:Mice, SCID; D010455:Peptides / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000473:pathology
D000951:Antigens, Neoplasm; D001324:Autoantigens; D019496:Cancer Vaccines; D010455:Peptides; D007073:Immunoglobulin E