Novel immunotherapy for Hematological Malignancy

血液恶性肿瘤的新型免疫疗法

• 批准号: 11557074
• 负责人: SAITO Hidehiko
• 金额: $ 8.38万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557074/
• 关键词: Vaccine; GVL; SEREX; CEV; SYK; Gene Gun; DNA Vaccine; PDGFR; チロシンリン酸化; マンノース; デンドリマー; DC; SFV

We have isolated leukemia specific fusion genes, CEV14-PDGFRβ and TEL-Syk, and mutant FLT3 Receptor. Also sixteen genes were isolated from leukemia genes using SEREX methods. These gene products have immnogenic motif and antibody response.DNA vaccination has emerged as an attractive approach for tumor immunotherapy. The technique of gold particle containing DNA bombardment by Herios Gene Gun (Bio-Rad) can be used to transfer genes to several tissues in vitro and in vivo. The aim of this study was to evaluate the efficiency of gene transfer in vitro and the potency of DNA vaccines in preventing and treating murine malignant tumor. We used the gene gun method to vaccinate C3H/He J mice intradermally with DNA vaccines containing the mutant FLT3R expression vector or the galactosidase expression vector in vivo. After immunization, mice were challenged intracutaneously on the abdomen with 1.5×10^7 tumorous 32D cells which transfected mutant FLT3R expression vector. Antitumor immunity was analyzed in both tumor prevention and tumor regression experiments. Mice immunized with mutant FLT3R expression vector prevented tumor and had antibody for tumor cells. In mice immunized with the galactosidase expression vector, tumor masses were palpable within 14 days after tumor challenge but disappeared. Control mice developed palpable and progressively growing tumors.

我们已经分离到白血病特异性融合基因CEV14-PDGFRβ和TEL-Syk，以及突变的Flt3受体。用SEREX方法从白血病基因中分离出16个基因。这些基因产物具有免疫原性和抗体反应性。DNA疫苗已成为肿瘤免疫治疗的一种有吸引力的方法。Herios基因枪轰击含有DNA的金粒子(Bio-Rad)技术可以在体外和体内将基因转移到多种组织中。本研究的目的是评价体外基因转移的效率和DNA疫苗预防和治疗小鼠恶性肿瘤的效力。我们用基因枪法将含有突变的Flt3R表达载体或半乳糖苷酶表达载体的DNA疫苗皮下接种C3H/He J小鼠。免疫后，用1.5×10~(-7)个肿瘤32D细胞对小鼠进行皮下攻击，获得突变型Flt3R表达载体。在肿瘤预防实验和肿瘤消退实验中进行抗肿瘤免疫分析。用突变的Flt3R表达载体免疫的小鼠可预防肿瘤并产生抗肿瘤细胞抗体。在用半乳糖苷酶表达载体免疫的小鼠中，肿瘤块在肿瘤攻击后14天内可触及，但已消失。对照组小鼠出现了可触及并逐渐生长的肿瘤。

项目成果

M Murata, N Emi, N Hirabayashi, M Hamaguchi, S Goto, A Wakita, M Tanimoto, H Saito, Y Kodera, Y Morishita for the Nagoya Blood and Marrow Transplantation Group: "No significant association between HA-1 incompatibility and developing acute graft-versus-hos

名古屋血液和骨髓移植组的 M Murata、N Emi、N Hirabayashi、M Hamaguchi、S Goto、A Wakita、M Tanimoto、H Saito、Y Kodera、Y Morishita：“HA-1 不相容性与急性发作之间没有显着关联

Tomita, A., Towatari, M., Tsuzuki, S., Hayakawa, F., Kosugi, H., Tamai, K., Miyazaki, T., Kinoshita, T.and Saito, H.: "c-Myb acetylation at the carboxyl-terminal conserved domain by transcriptional co-activator p300."Oncogene. 19. 444-451 (2000)

Tomita, A.、Towatari, M.、Tsuzuki, S.、Hayakawa, F.、Kosugi, H.、Tamai, K.、Miyazaki, T.、Kinoshita, T. 和 Saito, H.：“c-Myb 乙酰化

H.Mizuno,N.Emi,H.Saito, et al: "Successful Culture and Sustainability In Vivo of Gene-modified Human Oral Mucosal Epithelium.."Hum Gene Ther. 10. 825-830 (1999)

H.Mizuno、N.Emi、H.Saito 等人：“基因修饰的人口腔粘膜上皮的体内成功培养和可持续性..”Hum Gene Ther。

恵美宣彦: "遺伝子治療 開発研究ハンドブック"エヌ・ティ・エス. 10 (1999)

Nobuhiko Emi：《基因治疗开发研究手册》NTS 10 (1999)。

Kuno Y,Abe A,Emi N,Iida M,M,Tanimoto M,and Saito H: "Constitutive kinase activation of the TEL-Syk fusion in myelodysplastic syndrome with t(9;12)(q22;p12)."Blood.. (In press). (2001)

Kuno Y、Abe A、Emi N、Iida M、M、Tanimoto M 和 Saito H：“t(9;12)(q22;p12) 骨髓增生异常综合征中 TEL-Syk 融合的组成型激酶激活。”血液。