2006 Fiscal Year Final Research Report Summary
Clinical studies of dendritic cell therapy for malignancies and their evaluation
| Project/Area Number |
16390198
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General internal medicine (including Psychosomatic medicine)
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YAMASHITA Naohide The University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (90174680)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAOKA Takashi The University of Tokyo, Institute of Medical Science, Lecturer, 医科学研究所, 講師 (80241256)
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| Project Period (FY) |
2004 – 2006
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| Keywords | dendritic cell / CAII / endothelial cells / malignant melanoma / tumor-associated antigen |
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| Research Abstract |
Recent progress of imagings and endoscopy enables us to detect cancers at early stages, which has brought out favorable prognosis of early cancers. However, prognosis of advanced cancers is not always good in spite of recent advances in medical technologies and regimens. For such intractable malignancies development of new therapies are desired and much attention has been paid to cancer immunotherapy using dendritic cells (DC). We have carried out DC therapy in ten stage IV melanoma patients and six thyroid cancer patients with distant metastasis. We used tumor lysate as tumor antigen. In the melanoma study one patient was stable disease, two, mixed response, and seven, progressive disease. In the thyroid study two patients were stable disease and four, progressive disease. In two melanoma patients who showed mixed response shrinkage or disappearance of metastatic tumors with massive necrosis occurred. In this study, we found a 29-kDa protein against which antibody was elicited by dend
… More
ritic cell therapy in one of the two patients. Matrix-assisted laser desorption ionization-time of flight/mass spectrometry analysis of the protein isolated by two-dimensional electrophoresis combined with Western blots revealed that the 29-kDa protein was carbonic anhydrase II (CA-II). Immunohistochemistry of the tumors and normal tissues showed that CA-II was expressed in the tumor vessel but not in normal vessel endothelium. CA-II expression in tumor endothelium was observed as well in other cancers including esophageal, renal, and lung cancers. In an in vitro angiogenesis model, CA-II expression of normal human vein endothelial cells was significantly up-regulated when cells were cultured in the acidic and hypoxic conditions indicative of a tumor environment. These findings suggest that CA-II is a tumor vessel endothelium-associated antigen in melanoma and other cancers, and elicitation of serum anti-CA-II antibody by dendritic cell therapy may be associated with good clinical outcome including tumor reduction. Less
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[Journal Article] Results of a phase I clinical study using dendritic cell vaccinations for thyroid cancer.2007
Author(s)
K.Kuwabara, T.Nishishita, M.Morishita, N.Oyaizu, S.Yamashita, T.Kanematsu, T.Obara, Y.Mimura, Y.Inoue, M.Kaminishi, K.Koko, N.Amino, M.Kitaoka, K.Ito, A.Miyauchi, S.Noguchi, K.Uchimaru, E.Akagawa, N.Watanabe, TA.Takahashi, K.Sato, T.Inazawa, T.Nakaoka, N.Yamashita
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] TRAIL-transduced dendritic cells protect mice from acute graft-versus-host disease and leukemia relapse.2005
Author(s)
Sato, K., Nakaoka, T., Yamashima, N., Yagita, H., Kawasaki, H., Morimoto, C., Baba, M., Matsuyama, T.
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Journal Title
J.Immunol. 174
Pages: 4025-33
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Frequent immune responses to a cancer/testis antigen CAGE in patients with microsatellite instability-positive endometrial cancer.2005
Author(s)
T.Iwata, T.Fujita, N.Hirao, Y.Matsuzaki, T.Okada, H.Mochimaru, N.Susumu, E.Matsumoto, K.Sugano, N.Yamashita, S.Nozawa, Y.Kawakami
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Journal Title
Clin.Cancer Res. 11
Pages: 3949-57
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Carbonic anhydrase-II is a tumor vessel endothelium-associated antigen targeted by dendritic cell therapy.2005
Author(s)
K.Yoshiura, T.Nakaoka, T.Nishishita, K.Sato, A.Yamamoto, S.Shimada, T.Saida, Y.Kawakami, T.A.Takahashi, H.Fukuda, S.Imajoh-Ohmi, N.Oyaizu, N.Yamashita
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Journal Title
Clin.Cancer Res. 11
Pages: 8201-7
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Phase I Study of Autologous Tumor Vaccines Transduced with the GM-CSF Gene in Four Patients with Stage IV Renal Cell Cancer in Japan : Clinical and Immunological Findings.2004
Author(s)
K.Tani, M.Azuma, Y.Nakazaki, N.Oyaizu, H.Hase, J.Ohata, K.Takahashi, M.OiwaMonna, K.Hanazawa, Y.Wakumoto, K.Kawai, M.Noguchi, Y.Soda, R.Kunisaki, K.Watari, S.Takahashi, U.Machida, N.Satoh, A.Tojo, T.Maekawa, M.Eriguchi, S.Tomikawa, H.Tahara, Y.Inoue, H.Yoshikawa, Y.Yamada, A.Iwamoto, H.Hamada, N.Yamashita, K.Okumura, T.Kakizoe, H.Akaza, M.Fujime, S.C.Dale Ando, R.Mulligan, S.Asano
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Journal Title
Mol.Therapy 10
Pages: 799-816
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Inhibitory effect of low-dose estrogen on neointimal formation after balloon injury of rat carotid artery.2004
Author(s)
Watanabe, T., Miyahara, Y., Akishita, M., Nakaoka, T., Yamashita, N., Iijima, K., Kim, H., Kozaki, K., Ouchi, Y.
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Journal Title
Eur.J.Pharmacol. 502
Pages: 265-270
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Caveolin-1, Id3a and two LIM protein genes are upregulated by estrogen in vascular smooth muscle cells.2004
Author(s)
Watanabe, T., Akishita, M., Nakaoka, T., He, H., Miyahara, Y., Yamashita, N., Wada, Y., Aburatani, H., Yoshizumi, M., Kozaki, K., Ouchi, Y.
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Journal Title
Life Sci. 75
Pages: 1219-29
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A potential pro-angiogenic cell therapy with human placenta-derived mesenchymal cells.2004
Author(s)
Nishishita, T., Ouchi, K., Zhang, X., Inoue, M., Inazawa, T., Yoshiura, K., Kuwabara, K., Nakaoka, T., Watanabe, N., Igura, K., Takahashi, T.A., Yamashita, N.
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Journal Title
Biochem.Biophysic Res.Commun. 325
Pages: 24-31
Description
「研究成果報告書概要(欧文)」より
