Peptide vaccination for patients with melanoma and other types of cancer based on pre-existing peptide-specific ctotoxic T-lymphocyte precursors in the periphery.
Identification of antigenic peptides expressed on cancer cells enables us to treat cancer patients with peptide-based immunotherapy. Although optimal protocols for peptide-based vaccines have not yet been elucidated, boosting the immune system could be a better approach than priming the immune system to elicit prompt and potent peptide-specific T-cell responses in cancer patients. With this possibility in mind, the authors undertook a clinical trial in which cancer patients were vaccinated with peptides (maximum 4) after confirmation of pre-existing peptide-specific cytotoxic T-lymphocyte (CTL) precursors in the periphery. Fourteen patients (seven with melanoma and seven with other types of cancer) positive for either HLA-A24 or HLA-A2 were enrolled in this study. Fourteen and 16 peptides were used to screen for HLA-A24+ and HLA-A2+ patients, respectively. The vaccination was well tolerated, and the only adverse effects were local pain and fever. Kinetic analysis revealed that peptide-reactive CTLs increased after peptide vaccination in 7 of 14 patients. Immunoglobulin G (IgG) reactive to the administered peptides was detected in 2 patients before vaccination, although it became detectable in 8 of the other 12 patients after the peptide vaccination. Stable disease for more than 6 months was observed in five patients (one with melanoma and four with other types of cancer); all of these patients showed increased levels of peptide-specific IgG. These results indicate that peptide vaccination of patients showing evidence of pre-existing peptide-specific CTL precursors can be applied in further clinical trials aimed at the treatment of melanoma and other types of cancer.
Tanaka
Shoko
S
Department of Dermatology, Kurume University of School of Medicine, Fukuoka, Japan.
Harada
Mamoru
M
Mine
Takashi
T
Noguchi
Masanori
M
Gohara
Rumi
R
Azuma
Koichi
K
Tamura
Mayumi
M
Yamada
Akira
A
Morinaga
Akiko
A
Nishikori
Misa
M
Katagiri
Kazuko
K
Itoh
Kyogo
K
Yamana
Hideaki
H
Hashimoto
Takashi
T
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry; D019496:Cancer Vaccines / Q000737:chemistry; D002860:Chromium Radioisotopes / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D015234:HLA-A Antigens / Q000096:biosynthesis; D015789:HLA-A2 Antigen / Q000096:biosynthesis; D059871:HLA-A24 Antigen; D006801:Humans; D006969:Hypersensitivity, Immediate; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods; D007700:Kinetics; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D002860:Chromium Radioisotopes; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G; D010455:Peptides