title: Immunological evaluation of personalized peptide vaccination for patients with histologically unfavorable carcinoma of unknown primary site.
abstract: The immunological characteristics of carcinoma of unknown primary site (CUP) are not well established due to inclusion of heterogeneous types of metastatic tumors with the absence of any detectable primary site. We evaluated the immune responses in patients with histologically unfavorable CUP during personalized peptide vaccination (PPV). Ten patients with histologically unfavorable CUP who had been treated by PPV after chemotherapy failure were analyzed. In PPV treatment, up to four human leukocyte antigen-matched peptides of a total 31 peptides were selected according to preexisting host immunity before vaccination and administered subcutaneously. Peptides derived from the Lck antigen were most often chosen for use among all patients. CTL responses were increased in 8 of the 10 and 5 of the five patients tested at the end of the first and second PPV cycles, respectively. Increases in humoral responses after vaccination, including IgG, IgG1, IgG3, IgA, and IgM, were observed against not only the vaccinated peptides but also the non-vaccinated peptides. Severe adverse events due to PPV were not observed. Median overall survival was 13.9 months (95 % CI 4.0-22.5 months). PPV activated both cellular and humoral immune responses to short peptides derived from CTL epitopes in the majority of CUP patients. PPV with Lck-derived peptides may be a feasible, new treatment modality for histologically unfavorable CUP patients due to its safety and strong ability to boost immune responses, although its clinical efficacy remains to be investigated in larger-scale trials.
authors.affiliation: Cancer Vaccine Center, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan.|Clinical Research Division, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, 830-0011, Japan.|Department of Molecular and Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Sakamoto
authors.affiliation: Cancer Vaccine Center, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yutani
authors.affiliation: Cancer Vaccine Center, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shichijo
authors.affiliation: Department of Surgery, Nagasaki University Graduate Biomedical Science, Nagasaki, Japan.
authors.forename: Michi
authors.initials: M
authors.lastname: Morita
authors.affiliation: Cancer Vaccine Division, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Cancer Vaccine Center, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
authors.affiliation: Cancer Vaccine Center, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan. noguchi@med.kurume-u.ac.jp.|Clinical Research Division, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, 830-0011, Japan. noguchi@med.kurume-u.ac.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D019008:Drug Resistance, Neoplasm; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D056724:Immunity, Humoral; D007167:Immunotherapy / Q000379:methods*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009382:Neoplasms, Unknown Primary / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D010446:Peptide Fragments / Q000378:metabolism*; D057285:Precision Medicine; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
keywords: Cancer immunotherapy; Carcinoma of unknown primary site; Metastasis; Personalized peptide vaccine; Unfavorable subsets