Percutaneous peptide immunization via corneum barrier-disrupted murine skin for experimental tumor immunoprophylaxis.
H-2K(b)-restricted tumor epitope peptides, including tyrosinase-related protein 2 residues 181-188 (TRP-2) and connexin 37 residues 52-59 (MUT1), were applied to permeability barrier-disrupted C57BL/6 (B6) mouse skin from which the stratum corneum of the epidermis had been removed by tape-stripping. This procedure primed tumor-specific cytotoxic T lymphocytes (CTLs) in the lymph nodes and spleen, protected mice against subsequent challenge with corresponding tumor cells, and suppressed the growth of established tumors. Preventive and therapeutic effectiveness was correlated with the frequency of tumor-specific CTL precursors. MHC class II Ia(b+) cells separated from tape-stripped skin, compared with those from intact skin, exhibited a strong antigen-presenting capacity for CTL, suggesting that CTL expansion after peptide application is primarily mediated by epidermal Langerhans cells. Thus, percutaneous peptide immunization via barrier-disrupted skin provides a simple and noninvasive means of inducing potent anti-tumor immunity which may be exploited for cancer immunotherapy.
Seo
N
N
Department of Dermatology, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-3192, Japan. seo445@hama-med.ac.jp
Tokura
Y
Y
Nishijima
T
T
Hashizume
H
H
Furukawa
F
F
Takigawa
M
M
D000279:Administration, Cutaneous; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D017630:Connexins / Q000276:immunology; D000939:Epitopes; D006183:H-2 Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007114:Immunization / Q000379:methods*; D007167:Immunotherapy / Q000379:methods*; D019746:Intramolecular Oxidoreductases / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009842:Oligopeptides / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D012867:Skin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D000097006:Gap Junction alpha-4 Protein
D000951:Antigens, Neoplasm; D017630:Connexins; D000939:Epitopes; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D019746:Intramolecular Oxidoreductases; D009842:Oligopeptides; D010455:Peptides; D000097006:Gap Junction alpha-4 Protein; C032876:H-2Kb protein, mouse; C096894:MUT 1 peptide; C042501:dopachrome isomerase