Development of Dendritic Cell Vaccine Immunotherapy of Cancer Targeting MUC1 Mucin and Its Clinical Application

• Project/Area Number: 13671380
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Shiga University of Medical Sicence
• Principal Investigator: SAWAI Satoru (2002) Shiga University of Medical Science, Department of Surgery Associate Professor, 医学部, 助手 (60335172); 渡田 正二 (2001) 滋賀医科大学, 医学部, 助手 (90191816)
• Co-Investigator(Kenkyū-buntansha): KONTANI Keiichi Shiga University of Medical Science, Department of Surgery Associate Professor, 医学部, 助手 (90314153) ; FUJINO Shozo Shiga University of Medical Science, Department of Surgery Assistant Professor, 医学部, 助教授 (10209075) ; 澤井 聡 滋賀医科大学, 医学部, 助手 (60335172)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: dendritic cell / cancer vaccine / MUC1 / immunotherapy / 癌抗原 / MUC1 / 樹状細胞ワクチン / 癌免疫療法 / 癌ワクチン

Research Abstract

Employing dendritic cells (DCs) for cancer vaccination has been reported effective in suppressing cancer progression. This is because the DCs expressing high levels of MHC and co-stimulatory molecules are capable of activating tumor-specific cytotoxic T lymphocytes (CTLs) efficiently as antigen-presenting cells. In this study, we analyzed the ability of DCs to elicit tumor-specific CTLs and to suppress cancer progression by targeting MUC1 mucin highly expressed on breast cancer cells.
DCs induced from 4 patients with advanced breast cancer were loaded with MUC1 core peptides or cell lysate from MUC1-positive breast cancer cells. Tumor-specific CTLs induced from peripheral blood lymphocytes (PBLs) of the patients by in vitro stimulation with the antigen-loaded DCs were examined for their MUC1-specificity. To assess the ability of the loaded DCs to suppress tumor growth, they were inoculated at least three times into the patients.
The induced CTLs exhibited the cytotoxic activity or cytokine production in response to the MUC1 antigens. The PBLs obtained after DC vaccinations acquired MUC1-specific immune responses in all the patients with MUC1-positive tumors. The PBLs from a MUC1-negative patient did not show tumor-specific immunity. The tumor marker levels declined in all the MUC1-positive patients.
MUC1-specific CTLs can be induced using autologous DCs loaded with MUC1 antigens both in vitro and in vivo. The DC vaccination targeting MUC1 mucin is expected to be useful for anti-cancer immunotherapy.

Research Products

• [Publications] Kontani, K, Sawai, S., Hanaoka, J., Ichinose, M., Tezuka, N., Inoue, S., Fujino, S.: "Involvement of Granzyme B and Perform Produced by Tumor-Infiltrating Lymphocytes in Suppressing Metastasis of Cancer Cells to Regional Nodes in Patients with Breast and Lung Cancers"Eur. J. Surg. Oncol. 27. 180-186 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kontani, K., Taguchi, O., Narita, T., Izawa, M., Hiraiwa, N., Zenita, K., Takeuchi, T., Murai, H., Miura, S., Kannagi, R.: "Modulation of MUC1 mucin as an escape mechanism of breast cancer cells from autologous cytotoxic T-lymphocytes"Br. J. Cancer. 84(9). 1258-1264 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 紺谷桂一, 澤井聡, 花岡淳, 井上修平, 藤野昇三: "DCと癌抗原MUC1"Surgical Frontier. 17(2). 76-78 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kontani,K., Sawai,S., Hanaoka,J., Ichinose,M., Tezuka,N., Inoue,S., Fujino,S.: "Involvement of Granzyme B and Perforin Produced by Tumor-Infiltrating Lymphocytes in Suppressing Metastasis of Cancer Cells to Regional Nodes in Patients with Breast and Lung Cancers"Eur.J.Surg.Oncol.. 27. 180-186 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kontani,K., Taguchi,0., Narita,T., Izawa,M., Hiraiwa,N., Zenita,K., Takeuchi,T., Murai,H., Miura,S., Kannagi,R.: "Modulation of MUC1 mucin as an escape mechanism of breast cancer cells from autologous cytotoxic T-lymphocytes"Br.J.Cancer. 84(9). 1258-1264 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kontani, K., Taguchi, O., Sawai, S., et al.: "Novel vaccination protocol consisting of injecting MUC1 DNA and non-primed dendritic cells at the same region greatly enhanced MUC1-specific anti-tumor immunity in a murine model."Cancer Gene Therapy. 9・4. 330-337 (2002)