title: Immunological evaluation of peptide vaccination for cancer patients with the HLA-A26 allele.
abstract: To develop a peptide vaccine for cancer patients with the HLA-A26 allele, which is a minor population worldwide, we investigated the immunological responses of HLA-A26(+) /A26(+) cancer patients to four different CTL epitope peptides under personalized peptide vaccine regimens. In personalized peptide vaccine regimens, two to four peptides showing positive peptide-specific IgG responses in pre-vaccination plasma were selected from the four peptide candidates applicable for HLA-A26(+) /A26(+) cancer patients and administered s.c. Peptide-specific CTL and IgG responses along with cytokine levels were measured before and after vaccination. Cell surface markers in PBMCs and plasma cytokine levels were also measured. In this study, 21 advanced cancer patients, including seven lung, three breast, two pancreas, and two colon cancer patients, were enrolled. Their HLA-A26 genotypes were HLA-A26:01 (n = 24), HLA-A26:03 (n = 10), and HLA-A26:02 (n = 8). One, 14, and 6 patients received two, three, and four peptides, respectively. Grade 1 or 2 skin reactions at the injection sites were observed in the majority of patients, but no severe adverse events related to the vaccination were observed. Peptide-specific CTL responses were augmented in 39% or 22% of patients after one or two cycles of vaccination, respectively. Notably, peptide-specific IgG were augmented in 63% or 100% of patients after one or two cycles of vaccination, respectively. Personalized peptide vaccines with these four CTL epitope peptides could be feasible for HLA-A26(+) advanced cancer patients because of their safety and higher rates of immunological responses.
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.|Cancer Vaccine Center, Kurume University, Kurume, Japan.|Department of Molecular and Internal Medicine School of Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Sakamoto
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsueda
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Shinzo
authors.initials: S
authors.lastname: Takamori
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Uhi
authors.initials: U
authors.lastname: Toh
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Noguchi
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yutani
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shichijo
authors.affiliation: Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Fukuoka, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Urology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Suekane
authors.affiliation: Department of Gynecology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Kouichiro
authors.initials: K
authors.lastname: Kawano
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan.|Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sasada
authors.affiliation: Department of Molecular and Internal Medicine School of Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Department of Molecular and Internal Medicine School of Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume, Japan.
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D012189:Retrospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C482586:BTLA protein, human; D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines; D015234:HLA-A Antigens; C039683:HLA-A*26 antigen; D007074:Immunoglobulin G; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; D022223:Vaccines, Subunit; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human
keywords: Cancer vaccines; HLA-A26; IgG; cytotoxic T-Lymphocytes; peptide vaccines