Application of allograft rejection for lung cancer treatment

• Project/Area Number: 16590741
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Niigata University
• Principal Investigator: YOSHIZAWA Hirohisa Niigata University, Medical and Dental Hospital, Associate Professo, 医歯学総合病院, 助教授 (50282984)
• Co-Investigator(Kenkyū-buntansha): KAGAMU Hiroshi Niigata University, Medical and Dental Hospital, Assistant, 医歯学総合病院, 助手 (30418686) ; 塚田 弘樹 新潟大学, 医歯学総合病院, 助手 (50323986) ; 田中 洋史 新潟大学, 医歯学総合病院, 医員 ; 田中 純太 新潟大学, 医歯学総合病院, 医員
• Project Period (FY): 2004 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,300,000); Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: Dendritic cell / CD40 / CD137 / DR5 / 皮下腫瘍モデル / 制御性T細胞 / CD62 / 抗CD40抗体 / 防御免疫 / RNA導入

Research Abstract

In this project, 1)Ideal antigen source and conditioning of dendritic cells (DC) 2) Application of tumor-DC cell fusion 3) Ideal condition of allogenic bone marrow transplantation (ABMT) 4)Application of apoptotic tumor cell for antigen source, for DC cancer immunotherapy (DCI) were investigated.
1) Total RNA extracted from tumor cells were introduced to DC using RNA Transmessenger Kit. Transcribed GFP mRNA transfection efficiency (7.2%) was observed. Stimulation with anti-CD40 mAb as maturation signal, 1 hr after RNA pulse for 3 hrs, resulted in efficient induction of antitumor immune response.
2) DC was electrically fused with D5 tumor cells using BTX electric pulse generator. Fusion efficiency was approximately 50%. Intra-lymph-nodal injection of fusion cells in mice bearing D5 pulmonary metastases resulted in significant reduction of the metastasis. Also, potent effector cells were generated in vitro from naive spleen cells when stimulated with the fusion cells.
3) Optimal dose of total body irradiation (TBI) for conditioning of ABMT-DCI was examined. Optimal dose of TBI was found to be 800-1000R.
4) Induction of tumor-cell apoptosis by an agonistic monoclonal antibody to DR5, the apoptosis-inducing receptor for TNF- related apoptosis-inducing ligand (TRAIL), combined with T-cell activation by agonistic monoclonal antibodies to the costimulatory molecules CD40 and CD137, potently and rapidly stimulated tumor-specific effector CD8+ T cells capable of eradicating preestablished tumors.

Research Products

• [Journal Article] Eradication of established tumors in mice by a rationally combined antibody-based therapy (2006)
  • Author(s): Uno, T., T.Takeda, Y.Kojima, H.Yoshizawa et al.
  • Journal Title: Nature Medicine 12 Pages: 693-698
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Eradication of established tumors in mice by a rationally combined antibody-based therapy (2006)
  • Author(s): Uno, T., T.Takeda, Y.Kojima, H.Yoshizawa, H.et al.
  • Journal Title: Nature Medicine 12 Pages: 693-698
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Eradication of established tumors in mice by a rationally combined antibody-based therapy (2006)
  • Author(s): Uno, T., T.Takeda Y.Kojima H.Yoshizawa, H.et al.
  • Journal Title: Nature Medicine 12 Pages: 693-698
• [Journal Article] Both Regulatory T Cells and Antitumor Effector T Cells Are Primed in the Same Draining Lymph Nodes during Tumor Progression. (2005)
  • Author(s): Hiura, T., Yoshizawa.H.et al.
  • Journal Title: Journal of Immunology 175 Pages: 5058-5066
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Contribution of aspirin-intolerant asthma to near fatal asthma based on a questionnaire survey in Niigata Prefecture, Japan. (2005)
  • Author(s): Yoshimine, F., H.Yoshizawa et al.
  • Journal Title: Respirology 10 Pages: 477-484
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Gender diffrences in susceptibility of asthma to active smoking. (2005)
  • Author(s): Satoh, H., H.Yoshizawa, et al.
  • Journal Title: Allergollogy International 54 Pages: 401-410
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Facial axis angle as a risk factor for obstructive sleep apnea. (2005)
  • Author(s): Kubota, Y., H.Yoshizawa, et al.
  • Journal Title: Internal Medicine 44 Pages: 805-810
  • NAID: 130000076340
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Both Regulatory T Cells and Antitumor Effector T Cells Are Primed in the Same Draining Lymph Nodes during Tumor Progression. (2005)
  • Author(s): Hiura, T., Kagamu, H., Miura, S., Ishida, A., Tanaka, H., Tanaka, J., Gejyo, F., Yoshizawa, H.
  • Journal Title: Journal of Immunology 175 Pages: 5058-5066
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Contribution of aspirin-intolerant asthma to near fatal asthma based on a questionnaire survey in Niigata Prefecture, Japan. (2005)
  • Author(s): Yoshimine, F., T.Hasegawa, E.Suzuki, M.Terada, T.Koya, A.Kondoh, M.Arakawa, H.Yoshizawa, F.Gejyo.
  • Journal Title: Respirology 10 Pages: 477-484
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Gender diffrences in susceptibility of asthma to active smoking. (2005)
  • Author(s): Satoh, H., T.Hasegawa, E.Suzuki, M.Terada, H.Nakayama, S.Toyabe, K.Akazawa, A.Kondo, M.Arakawa, H.Yoshizawa, F.Gejyo.
  • Journal Title: Allergollogy International 54 Pages: 401-410
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Facial axis angle as a risk factor for obstructive sleep apnea. (2005)
  • Author(s): Kubota, Y., H.Nakayama, T.Takada, N.Matsuyama, K.Sakai, H.Yoshizawa, M.Nakamata, M.Satoh, K.Akazawa, E.Suzuki, F.Gejyo.
  • Journal Title: Internal Medicine 44 Pages: 805-810
  • NAID: 130000076340
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Short-term use of continuous positive airway pressure ameliorates glomerular hyperfiltration in patients with obstructive sleep apnoea syndrome. (2004)
  • Author(s): Kinebuchi, S., H.Yoshizawa, et al.
  • Journal Title: Clinical Science (Lond) 107 Pages: 317-322
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Questionnaire-based characterization of bronchial asthma in the elderly : Analysis in Niigata Prefecture, Japan. (2004)
  • Author(s): Hasegawa, T., H.Yoshizawa, et al.
  • Journal Title: Allergology International 53 Pages: 145-151
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 2004. Short-term use of continuous positive airway pressure ameliorates glomerular hyperfiltration in patients with obstructive sleep apnoea syndrome. (2004)
  • Author(s): Kinebuchi, S., J.J.Kazama, M.Satoh, K.Sakai, H.Nakayama, H.Yoshizawa, I.Narita, E.Suzuki, F.Gejyo.
  • Journal Title: Clinical Science (Lond) 107 Pages: 317-322
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 2004. Questionnaire-based characterization of bronchial asthma in the elderly : Analysis in Niigata Prefecture, Japan. (2004)
  • Author(s): Hasegawa, T., E.Suzuki, Y.Muramatsu, T.Koya, I.Mashima, A.Kondo, H.Takagi, K.Fujimori, M.Arakawa, H.Yoshizawa, F.Gejyo.
  • Journal Title: Allergology International 53 Pages: 145-151
  • Description: 「研究成果報告書概要(欧文)」より