2007 Fiscal Year Final Research Report Summary
preventive immunotherapy against virous-associated tumor by tumor-specific protein antigen
| Project/Area Number |
18591248
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Okayama University |
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Principal Investigator |
TSUJI Kazuhide Okayama University, HOSPITAL of MEDICINE and DENTISTRY, assistant professor (30304356)
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| Co-Investigator(Kenkyū-buntansha) |
IWATSUKI Keiji OKAYAMA UNIVERSITY, GRADUATE SCHOOL of MEDICINE, DENTISTRY and PHARMACEUTICAL SCIENCES, Professor (80126797)
NAKANISHI Gen OKAYAMA UNIVERSITY, HOSPITAL of MEDICINE and DENTISTRY, assistant professor (80314673)
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| Project Period (FY) |
2006 – 2007
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| Keywords | hydroa vacciniforme / Epstein-Barr virus / cancer vaccme / CTL / NK / T cell lymphoma / virus-specific protein antigen / regulatory T cell / immune tolerance |
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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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[Journal Article] Induction of immune response against NY-ESO-1 by CI1P-NYES0-1 vaccination and immune regulation in a melanoma patient2008
Author(s)
Kazubide, Thuji, Toshitada, Hamada, Akiko, Uenaka, Hisashi, Wada, Eiichi, Sato, Midori, Isobe, Kenji, Asagoe, Osamu, Yamasaki, Hiroshi, Shiku, Gerd, Ritter, Roger, Murphy, Eric W., HoVman, Lloyd, J., Old, Eiichi, Nakayama, Keiji, Iwatsuki
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Journal Title
Cancer Immunol Immunother
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans2007
Author(s)
Sakamoto, N., Tsuji, K., Muul, LM., Lawler, AM., Petricoin, EF., Candotti, F., Metcalf, JA., Tavel, JA., Lane, HC., Urba, WJ., Fox, BA., Varki. A., Lunney, JK., Rosenberg, AS
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Journal Title
Blood 110(2)
Pages: 501-8
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Recovery from Sezary syndrome following Mycobacterium avium spondylitis2007
Author(s)
Yamada, A., Yamasaki, O., Asagoe, K., Tsuji, K., Hamada, T., Ota, Y., Iwatsuki, K
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Journal Title
Br J Dermatol 157(6)
Pages: 1270-1
Description
「研究成果報告書概要(欧文)」より
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[Presentation] NY-ESO-1 Protein-Based Immunotherapy for Malignant Melanoma : Tumor Antigen-Specific T cell Responses and Suppressive Phenomenon2006
Author(s)
Tsuji, K., Hamada, T., Asagoe, K., Wada, H., Kawabata, R., Aji, T., Uenaka, A., Shiku, H., Nakayama, E., Iwatsuki, K
Organizer
36thAnnual European Society for Dermatological Research (ESDR) Meeting
Place of Presentation
Paris, France
Year and Date
20060907-09
Description
「研究成果報告書概要(欧文)」より
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