title: Induction of therapeutically relevant cytotoxic T lymphocytes in humans by percutaneous peptide immunization.
abstract: Percutaneous peptide immunization (PPI) is a simple and noninvasive immunization approach to induce potent CTL responses by peptide delivery via skin with the stratum corneum removed. After such a barrier disruption in human skin, epidermal Langerhans cells, although functionally matured through the up-regulation of HLA expression and costimulatory molecules, were found to emigrate with a reduced number of dendrites. CD8(+) populations binding to MHC-peptide tetramers/pentamers and producing IFN-gamma appeared in the blood after PPI with HLA class I-restricted antigenic peptides. PPI with melanoma-associated peptides reduced the lesion size and suppressed further development of tumors in four of seven patients with advanced melanoma. These beneficial effects were accompanied by the generation of circulating CTLs with in vitro cytolytic activity and extensive infiltration of tetramer/pentamer-binding cells into regressing lesions. PPI elicited neither local nor systemic toxicity or autoimmunity, except for vitiligo, in patients with melanoma. Therefore, PPI represents a novel therapeutic intervention for cancer in the clinical setting.
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. hiroyagi@hama-med.ac.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yagi
authors.forename: Hideo
authors.initials: H
authors.lastname: Hashizume
authors.forename: Takahiro
authors.initials: T
authors.lastname: Horibe
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yoshinari
authors.forename: Maki
authors.initials: M
authors.lastname: Hata
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohshima
authors.forename: Taisuke
authors.initials: T
authors.lastname: Ito
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takigawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Shibaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Naohiro
authors.initials: N
authors.lastname: Seo
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D010455:Peptides / Q000008:administration & dosage* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D007371:Interferon-gamma