| Budget Amount *help |
¥3,850,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
OKAYAMA UNIVERSITY HOSPITAL of MEDICINE and DENTISTRY, assistant professor We reported NY-ESO-1 protein-based immunotherapy for malignant melanoma: tumor antigen-specific T cell responses and suppressive phenomenon. Hycixophobized polysaccharide, maim (CHP) is a navel, simple protein delivery system, which is designed to tam complexes with soluble protein molecules. The truncated protein is processed by dendritic cells through a pathway similar to that for endogenous proteins. The NY-ESO-1 human tumor antigen is a "cancer-testis" antigen expressed by various neoplasms, including melanoma. We report a cam of malignant melanoma treated with the NY-ESO-1 protein formulated in CHP (CHP/ESO), according to Code of Ethics. A 50-year-old man with stage W (T4N3M1c) malignant melanoma was challenged by Sc. Injections of CHP/ESO vaccine every 2 weeks. A month afar treatment, multiple blister formation was observed on the metastatic lesions almost at the same time. Histological examination confirm
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ed the death of NY-ESO-1+ melanoma (PHs by TUNEL assay. CHP/ESO vaccine induced a gradual increase of NY-ESO-1-specific IgG1 in serum and a high CD8/CD4T cell ratio in serum and skin lesion. Using IPH-y secretion assays with synthetic overlapping peptides as monitors of T cell responses, we Smut increase in the number of NY-ESC-I.-specific CD4+ T calls and CD8+ T cells in circulation after vaccination. Despite having received a cancer vaccine, tumors continued to grow and the patient died of pulmonary failure due to multiple metastasis. Analysis of postvaccine lesions prom patient showed an increased number of CD25+FOXP3+ cells and tumor-associated macrophages, and an increased amount of IL-4 and IL-10 secretion in the blister fluid. Our observations indicate the commence of NY-ESO-1-specific immune response and immune suppression simultaneously, which may result in tumor progression and immune escape phenomenon.
In addition, we reported a novel, noninvasive method to detect EBV-encoded small RNA (EBER), Bam HI A rightward transcripts (BARTs) in the skin crusts and scales of such patients. Our procedure may be of use as a biomarker for EBV-associated cutaneous lesions, including hydroa vacciniforme, HMB, and NK/T-cell lymphomas. Less
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