2003 Fiscal Year Annual Research Report

抗体療法及びがんの前臨床試験研究

Research Project

Project/Area Number	12217127
Research Institution	Nagoya City University
Principal Investigator	上田龍三名古屋市立大学, 大学院・医学研究科, 教授 (20142169)
Co-Investigator(Kenkyū-buntansha)	吉川和宏愛知医科大学, 医学部, 講師 (60109759) 折戸悦郎名古屋市立大学, 大学院・医学研究科, 講師 (60204294) 佐藤滋樹名古屋市立大学, 大学院・医学研究科, 助教授 (80254283)
Keywords	抗体療法 / 前臨床試験 / 分子標的療法 / 抗体
Research Abstract	抗体を用いたがんの診断・治療法の開発のため前臨床試験を中心にtranslational researchを推進させながら以下の成果を得た。慢性B型肝炎患者血清を用いS遺伝子領域のRFLP法によるgenotype決定法を開発し、民族性、病態の進展、肝癌発症リスクと関わることを明らかにした。肺小細胞肺癌で発現するガングリオシドGD2に対するinterleukin2結合抗GD2抗体は強力なカスペース活性依存性アポトーシスを誘導し、マウス肺内転移モデルでも抗腫瘍効果を確認することができた。転座関連原がん遺伝子であるMUM1/IRF4に関わる下流分子をcDNAアレイにてスクリーニングし、Monokine induced by IFNγ(Mig)とFK506 binding Protein 3はMUM1の直接の標的遺伝子であることを明らかとし、さらにMigのレセプターであるCXCR3を標的とした中和抗体により増殖抑制効果を見出した。リモデリング抗体では変異EGFレセプター抗体、抗CD25抗体の単鎖抗体の作製に成功し、変異EGFレセプター抗体では脳内移植腫瘍に対し極めて高い集積性を確認し、ヒト抗体とのキメラ抗体を作製した。ケモカインレセプターCCR4では成人T細胞性白血病(ATL)のほか末梢性T細胞性リンパ腫でも高頻度に発現し予後不良因子であること、さらにATL及びT細胞系腫瘍検体で抗CCR4抗体が自己のエフェクター細胞を介したADCCによる増殖抑制効果を確認し,早期臨床試験への準備を展開した。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] Niwa, R, Ueda, R. et al.: "Defucosylated chimeric anti-CCR4 IgG1 with enhanced antibody-dependent cellular cytotoxicity shows potent thrapeutic activity to T cell leukemia and lymphoma."Cancer Res. (in press).
[Publications] Ozeki, K., Ueda., R.et al.: "Biological and clinical significance of the FLT3 transcript level in acute myeloid leukemia"Blood. (in press).
[Publications] Ding, J., Iida, S., Ueda, R.et al.: "Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin."Blood. (in press).
[Publications] Ishida, T., Iida S., Ueda, R.et al.: "Clinical significance of CCR4 expression in adult T-cell leukemia/lynphoma (ATLL):its close association with skin involvement and unfavorable outcome."Clin Cancer Res.. 9. 3625-3634 (2003)
[Publications] Sugauchi, F., Ueda, R.et al.: "Epidemiological and virological characteristics of hepatitis B virus genotype B having the recombination with genotype C."Gastroenterology. 124. 925-932 (2003)
[Publications] Minami, Y., Ueda, R.et al.: "Different antiapoptotic pathways between wild-type and mutated FLT3 : insights into therapeutic targets in leukemia."Blood. 102. 2969-2975 (2003)
[Publications] Okabe, M., Ueda, R.et al.: "API2-MALT1 fusion defines a distinctive clinicopathologic subtype in pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue"Am.J.Pathology. 162(4). 1113-1122 (2003)
[Publications] Ueda, R.: "Multistep tumorigenesis of multiple myeloma : its molecular delineation."Int.J.Hematology. 77. 207-212 (2003)
[Publications] Miura, K., Ueda, R.et al.: "Frequent occurrence of CCND1 deregulation in patients with early stages of plasma cell dyscrasia."Cancer Science. 94(4). 350-354 (2003)
[Publications] Ito, H., Sato, S., Ueda, R.et al.: "A limited association of OGG1 ser326Cys polymorphism for adenocarcinoma of the lung."J.Epidemiology. 12(3). 258-265 (2003)
[Publications] Kato, H., Orito, E., Ueda, R., et al.: "Regression of esophageal papillomatous polyposis caused by high-risk type human papilloma virus."J.Gastroenterol. 38. 579-583 (2003)
[Publications] Miyazaki, H., Sato, S., Ueda, R.et al.: "Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells."Clinical Immunology. 107. 198-201 (2003)
[Publications] Achiwa, H., Sato, S., Ueda, R.et al.: "Analysis of βtubulin gene alteration in human lung cancer cell lines."Cancer letters. 201. 211-216 (2003)

2003 Fiscal Year Annual Research Report

抗体療法及びがんの前臨床試験研究

Principal Investigator

上田 龍三 名古屋市立大学, 大学院・医学研究科, 教授 (20142169)

Research Products

[Publications] Niwa, R, Ueda, R. et al.: "Defucosylated chimeric anti-CCR4 IgG1 with enhanced antibody-dependent cellular cytotoxicity shows potent thrapeutic activity to T cell leukemia and lymphoma."Cancer Res. (in press).

[Publications] Ozeki, K., Ueda., R.et al.: "Biological and clinical significance of the FLT3 transcript level in acute myeloid leukemia"Blood. (in press).

[Publications] Ding, J., Iida, S., Ueda, R.et al.: "Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin."Blood. (in press).

[Publications] Ishida, T., Iida S., Ueda, R.et al.: "Clinical significance of CCR4 expression in adult T-cell leukemia/lynphoma (ATLL):its close association with skin involvement and unfavorable outcome."Clin Cancer Res.. 9. 3625-3634 (2003)

[Publications] Sugauchi, F., Ueda, R.et al.: "Epidemiological and virological characteristics of hepatitis B virus genotype B having the recombination with genotype C."Gastroenterology. 124. 925-932 (2003)

[Publications] Minami, Y., Ueda, R.et al.: "Different antiapoptotic pathways between wild-type and mutated FLT3 : insights into therapeutic targets in leukemia."Blood. 102. 2969-2975 (2003)

[Publications] Okabe, M., Ueda, R.et al.: "API2-MALT1 fusion defines a distinctive clinicopathologic subtype in pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue"Am.J.Pathology. 162(4). 1113-1122 (2003)

[Publications] Ueda, R.: "Multistep tumorigenesis of multiple myeloma : its molecular delineation."Int.J.Hematology. 77. 207-212 (2003)

[Publications] Miura, K., Ueda, R.et al.: "Frequent occurrence of CCND1 deregulation in patients with early stages of plasma cell dyscrasia."Cancer Science. 94(4). 350-354 (2003)

[Publications] Ito, H., Sato, S., Ueda, R.et al.: "A limited association of OGG1 ser326Cys polymorphism for adenocarcinoma of the lung."J.Epidemiology. 12(3). 258-265 (2003)

[Publications] Kato, H., Orito, E., Ueda, R., et al.: "Regression of esophageal papillomatous polyposis caused by high-risk type human papilloma virus."J.Gastroenterol. 38. 579-583 (2003)

[Publications] Miyazaki, H., Sato, S., Ueda, R.et al.: "Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells."Clinical Immunology. 107. 198-201 (2003)

[Publications] Achiwa, H., Sato, S., Ueda, R.et al.: "Analysis of βtubulin gene alteration in human lung cancer cell lines."Cancer letters. 201. 211-216 (2003)

上田龍三名古屋市立大学, 大学院・医学研究科, 教授 (20142169)