Development of anti-angiogenic therapy based on the analysis of patients responded to dendritic cell therapy

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390190
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: The University of Tokyo
• Principal Investigator: YAMASHITA Naohide The University of Tokyo, 医科学研究所, 教授 (90174680)
• Co-Investigator(Kenkyū-buntansha): NAKAOKA Takashi 東京大学, 医科学研究所, 講師 (80241256) ; WATANABE Tokumitsu 東京大学, 医科学研究所, 助教 (80401264)
• Project Period (FY): 2007 – 2009
• Keywords: 樹状細胞 / 腫瘍血管 / 発現解析 / hUVEC / 抗体

Research Abstract

We analyzed the melanoma patients who were treated with the dendritic cell therapy. In three patients who responded to this therapy the antibody to carbonic anhydrase II (CAII) was elevated after treatment. Immunohistochemical study revealed the expression of CAII specific to tumor vessel endothelium. Based on these findings this study was designed (1) to explore antibodies which specifically destruct the tumor vessel, and (2) to establish the immunotherapy using hUVECs which are differentiated similar to tumor vessel endothelium. We constituted cDNA library from melanoma tissue and expressed proteins, and thereafter screened with patients' sera. With regard to immunotherapy we conducted animal model study and found that immunization of tumor vessel endothelium significantly prolonged the life span of animals transplanted with melanoma cells.

Research Products

• [Journal Article] Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease. (2009)
  • Author(s): Sato K, Eizumi K, Fukaya T, Fujita S, Sato Y, Takagi H, Yamamoto M, Yamashita N, Hijikata A, Kitamura H, Ohara O, Yamasaki S, Saito T, Sato K
  • Journal Title: Blood 113 Pages: 4780-4789
• [Journal Article] Inhibition of B16 melanoma growth and metastasis in C57BL mice by vaccination with a syngeneic endothelial cell line. (2009)
  • Author(s): Yoshiura K, Nishishita T, Nakaoka T, Yamashita N, Yamashita N
  • Journal Title: J Exp Clin Cancer Res 28 Pages: 13-18
• [Journal Article] Regulatory dendritic cells protect against allergic airway inflammation in a murine asthmatic model. (2008)
  • Author(s): Fujita S, Yamashita N, Ishii Y, Sato Y, Sato K, Eizumi K, Fukaya T, Nozawa R, Takamoto Y, Yamashita N, Taniguchi M, Sato K
  • Journal Title: J Allergy Clin Immunol. 121 Pages: 95-104
• [Journal Article] Dnm3os, a Non-coding RNA, is Required for Normal Growth and Skeletal Development in Mice. (2008)
  • Author(s): Watanabe T, Sato T, Amano T, Kawamura Y, Kawamura N, Kawaguchi H, Yamashita N, Kurihara H, Nakaoka T
  • Journal Title: Dev. Dyn. 237 Pages: 3738-48
• [Journal Article] Results of a phase I clinical study using dendritic cell vaccinations for thyroid cancer. (2007)
  • Author(s): Kuwabara, K., Nishishita, T., Morishita, M., Oyaizu, N., Yamashita, S., Kanematsu, T., Obara, T., Mimura, Y., Inoue, Y., Kaminishi, M., Kaga, K., Amino, N., Kitaoka, M., Ito, K., Miyauchi, A., Noguchi, S., Uchimaru, K., Akagawa, E., Watanabe, N., Takahashi, TA, Sato, K., Inazawa, T., Nakaoka, T., Yamashita, N
  • Journal Title: Thyroid 17 Pages: 53-58
• [Journal Article] Regulatory dendritic cells protect against cutaneous chronic graft-versus-host disease mediated through CD4+CD25+Foxp3+ regulatory T cells. (2007)
  • Author(s): Fujita, S., Sato, Y., Sato, K., Eizumi, K., Fukaya, T., Kubo, M., Yamashita, N., Sato, K.
  • Journal Title: Blood 110 Pages: 3793-3803