Journal
BRITISH JOURNAL OF CANCER
Volume 87, Issue 7, Pages 796-804Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6600548
Keywords
immunotherapy; cancer; peptide vaccine; CTL-precursors; pre-vaccination
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Development of therapeutic vaccines is one of the major areas of tumour immunotherapy today. However, clinical trials of peptice-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 peptice-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. Peptice-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-1-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 peptice vaccine. (C) 2002 Cancer Research UK.
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