Detection of peptide-specific CTL-precursors in peripheral blood lymphocytes of cancer patients.
Development of therapeutic vaccines is one of the major areas of tumour immunotherapy today. However, clinical trials of peptide-based cancer vaccines have rarely resulted in tumour regression. This failure might be due to an insufficient induction of cytotoxic T lymphocytes in the current regimes, in which cytotoxic T lymphocytes-precursors in pre-vaccination peripheral blood mononuclear cells are not measured. Initiation of immune-boosting through vaccination could be better than that of immune-priming with regard to induction of prompt and strong immunity. If this is also the case for therapeutic vaccines, pre-vaccination measurement of peptide-specific cytotoxic T lymphocytes-precursors will be important. In the present study, we investigated whether cytotoxic T lymphocytes-precursors reacting to 28 kinds of peptides of vaccine candidates (13 and 15 peptides for HLA-A24(+) and HLA-A2(+) patients, respectively) were detectable in pre-vaccination peripheral blood mononuclear cells of 80 cancer patients. Peptide-specific cytotoxic T lymphocytes-precursors were found to be detectable in peripheral blood mononuclear cells of the majority of cancer patients (57 out of 80 cases, 71%). The mean numbers of positive peptides were 2.0 peptides per positive case. Peripheral blood mononuclear cells incubated with positive peptides, not with negative peptides, showed significant levels of HLA-class-I-restricted cytotoxicity to cancer cells. The profiles of positive peptides entirely varied among patients, and were not influenced by the cancer origin. These results may provide a scientific basis for the development of a new approach to cancer immunotherapy, e.g.) cytotoxic T lymphocytes-precursor-oriented peptide vaccine.
Maeda
Y
Y
Department of Immunology, Kurume University, 67 Asahi-machi, Kurume, 830-0011, Japan.
Hida
N
N
Niiya
F
F
Katagiri
K
K
Harada
M
M
Yamana
H
H
Kamura
T
T
Takahashi
M
M
Sato
Y
Y
Todo
S
S
Itoh
K
K
D000951:Antigens, Neoplasm / Q000276:immunology*; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D009369:Neoplasms / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D010455:Peptides; D007371:Interferon-gamma