Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide.
Immunogenicity of a long 20-mer NY-ESO-1f peptide vaccine was evaluated in a lung cancer patient TK-f01, immunized with the peptide with Picibanil OK-432 and Montanide ISA-51. We showed that internalization of the peptide was necessary to present CD8 T-cell epitopes on APC, contrasting with the direct presentation of the short epitope. CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination. Clonal analysis showed that B*35:01 and B*52:01-restricted CD8 T-cell responses were the two dominant responses. The minimal epitopes recognized by A*24:02, B*35:01, B*52:01 and C*12:02-restricted CD8 T-cell clones were defined and peptide/HLA tetramers were produced. NY-ESO-1 91-101 on A*24:02, NY-ESO-1 92-102 on B*35:01, NY-ESO-1 96-104 on B*52:01 and NY-ESO-1 96-104 on C*12:02 were new epitopes first defined in this study. Identification of the A*24:02 epitope is highly relevant for studying the Japanese population because of its high expression frequency (60%). High affinity CD8 T-cells recognizing tumor cells naturally expressing the epitopes and matched HLA were induced at a significant level. The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine. Characterization of CD8 T-cell responses in immunomonitoring using peptide/HLA tetramers revealed that multiple CD8 T-cell responses comprised the dominant response.
Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Shingo
S
Eikawa
Kazuhiro
K
Kakimi
Midori
M
Isobe
Kiyotaka
K
Kuzushima
Immanuel
I
Luescher
Yoshihiro
Y
Ohue
Kazuhiro
K
Ikeuchi
Akiko
A
Uenaka
Hiroyoshi
H
Nishikawa
Heiichiro
H
Udono
Mikio
M
Oka
Eiichi
E
Nakayama
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D017321:Clinical Trials, Phase I as Topic; D018604:Epitope Mapping; D005805:Genes, MHC Class I; D006801:Humans; D016233:Immunotherapy, Active; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology*; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C568699:NY-ESO-1 protein, human (91-110); D010446:Peptide Fragments