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Recent clinical trials of peptide vaccine for cancer patients have rarely resulted in tumor regression. One of the reasons for this failure could be an insufficient induction of anti-tumor responses in these regimens, in which peptide-specific memory cytotoxic T lymphocytes (CTLs) were not measured prior to vaccination. We investigated in this study whether pre-vaccination measurement of peptide-specific CTLs can provide any advantages in lung cancer patients receiving peptide vaccination with regard to safety and immunological responses. Ten patients with advanced lung cancer received vaccination with peptides under a regimen of CTL precursor-oriented vaccination, in which pre-vaccination peripheral blood mononuclear cells (PBMCs) were at first screened for reactivity in vitro to each of 14 peptides, followed by in vivo administration of only the reactive peptides. Profiles of the vaccinated peptides varied markedly among the 10 patients. This regimen was generally well-tolerated, although local skin reactions, diarrhea, and colitis were observed in 8, 2, and 1 patient, respectively. Increased CTL responses against the immunized peptides and tumor cells were observed in the post-vaccination PBMCs from 4 of 8 and 3 of 10 patients tested, respectively. Peptidespecific IgG became detectable in post-vaccination sera in 4 of 10 patients tested, and these 4 patients had a long progression-free survival. Furthermore, the median survival time of 9 patients with non-small cell lung cancer was 668.0 ± ± ± ±164.2 days. These results encourage further development of CTL precursor-oriented peptide vaccination for lung cancer patients. (Cancer Sci 2003; 94: 548-556) dentification of a large number of antigenic epitopes 1-9) recognized by cytotoxic T lymphocytes (CTLs) reacting to tumor cells has opened the door to clinical trials of peptide-based immunotherapy for cancer patients. [10][11][12][13][14][15][16] Many clinical trials of peptide-based immunotherapy for malignant melanoma and other epithelial tumors have been conducted in the past decade, but major clinical responses were rarely obtained in these clinical studies, including our trial of a cyclophilin B (CypB) peptide vaccination for advanced lung cancer patients 17) and a SART3 peptide vaccination for advanced colorectal cancer patients.18) One reason for this failure to obtain tumor regression could be an insufficient induction of anti-tumor responses in these vaccine regimens, in which peptide-specific memory T cells were not measured in pre-vaccination peripheral blood mononuclear cells (PBMCs). We have speculated that vaccination based on information from pre-vaccination measurement of peptide-specific CTLs in the circulation might induce potent anti-tumor immune responses in cancer patients. This hypothesis is based on the assumption that initiation of immune-boosting of CTLs through peptide vaccination could be more effective than immune-priming of naive T cells with regard to induction of prompt and strong immunity to both the peptide and tumor cells. We ha...

Purpose: The purpose of this work was to provide a scientific basis for specific immunotherapy of colon cancer.Experimental Design: This study focused on identification of colon tumor-associated antigens and HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes (CTLs) generated from tumor-infiltrating lymphocytes of a colon cancer patient. A gene expression cloning method was used to identify genes coding for tumor antigens. Fifty-six peptides with HLA-A2-binding motifs encoded by these proteins were examined for their ability to induce HLA-A2-restricted and tumor-reactive CTLs.Results: We identified the following three genes coding for proliferation-related proteins: thymidylate synthase (TYMS), which is involved in chemoresistance (

We examined risk factors for coronary heart disease (CHD) by ambulatory blood pressure (BP) monitoring in 72 diabetic hypertensives who were hospitalized for the educational program. The patients were divided into two groups (CHD group, 19 subjects; and non-CHD group, 53 subjects) along with or without co-existing CHD. On ambulatory BP monitoring, no significant differences were found between the groups regarding BP values through the day. However, the CHD group had a significantly greater BP variability than non-CHD group. The result of logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor for CHD.

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