Development for DNA vaccination against viral hepatitis recurrence after the liver transplantation using gene gun

使用基因枪开发针对肝移植后病毒性肝炎复发的DNA疫苗接种

• 批准号: 13470261
• 负责人: KOBAYASHI Eiji
• 金额: $ 6.91万
• 依托单位: Jichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470261/
• 关键词: Viral hepatitis; Liver transplantation; DNA vaccine; Non-specific immunosuppressant; KF506; Hydrodynamic DNA injection; Gene gun; 非特異的免没抑制剤; B型肝炎; ラット

The DNA vaccine represents a novel means of expressing antigens in vivo for the generation of both humoral and cellular immune responses. It has elicited protective immunity in a number of preclinical models of diseases. In the light of efficient DNA vaccination, particle-mediated gene transfer (gene gun) was one of the most immunization methods. Although recent advances in gene therapy have improved a number of recombinant viral vectors, their recombinant viruses may remain restricted from the standpoint of clinical application because of the risk of systemic complications in the transplant recipient. In particular, we demonstrated a preventive potential of DNA vaccine against hepatitis B virus in a rat model of the liver transplantation. Preliminary evidence in this preclinical model suggests that the combination of an immunized partial liver graft with FK506 strongly enhance antibody production against hepatitis B virus surface antigen. Therefore, DNA immunization could provide an effective strategy for introducing protective immune response against infectious diseases in the liver transplantation.

DNA疫苗代表了一种在体内表达抗原以产生体液和细胞免疫应答的新方法。它在许多疾病的临床前模型中引起保护性免疫。鉴于DNA疫苗的有效性，粒子介导的基因转移（基因枪）是最常用的免疫方法之一。尽管基因治疗的最新进展已经改进了许多重组病毒载体，但由于移植受体中的全身性并发症的风险，从临床应用的观点来看，它们的重组病毒可能仍然受到限制。特别是，我们证明了DNA疫苗对肝移植大鼠模型中的B型肝炎病毒的预防潜力。该临床前模型的初步证据表明，免疫的部分肝移植物与FK506的组合强烈增强了抗B肝炎病毒表面抗原的抗体产生。因此，DNA免疫可以为肝移植中引入抗感染性疾病的保护性免疫应答提供一种有效的策略。

项目成果

Ajiki T, et al.: "Long-lasting gene expression by particle-mediated Intramuscular transfection modified with bupivacaine : Combinatorial gene therapy with IL-12 and IL-18 cDNA against rat sarcoma at distant site."Cancer Gene Therapy. 10. 318-329 (2003)

Ajiki T 等人：“布比卡因修饰的颗粒介导肌内转染实现持久基因表达：使用 IL-12 和 IL-18 cDNA 对抗远处大鼠肉瘤的组合基因治疗。”癌症基因治疗。

Nakamura M, et al.: "DNA immunization of the grafted liver by particle-mediated gene gun."Transplantation. 76(9). 1368-1375 (2003)

Nakamura M 等人：“通过粒子介导的基因枪对移植肝脏进行 DNA 免疫。”移植。

Ajiki T, et al.: "Long-lasting gene expression by particle-mediated intramuscular transfection modified with bupivacaine : combinatorial gene therapy with IL-12 and IL-18 cDNA against rat sarcoma at a distant site."Cancer Gene Ther. 10(4). 318-329 (2003)

Ajiki T 等人：“通过用布比卡因修饰的颗粒介导的肌内转染实现持久基因表达：使用 IL-12 和 IL-18 cDNA 对抗远处大鼠肉瘤的组合基因治疗。”Cancer Gene Ther。

Wang J, et al.: "Gene gun-mediated oral mucosal transfer of interleukin 12 cDNA coupled with an irradiated melanoma vaccine in a hamster model : successful treatment of oral melanoma and distant skin lesion."Cancer Gene Ther. 8(10). 795-712 (2001)

Wang J 等人：“基因枪介导的白细胞介素 12 cDNA 口腔粘膜转移与仓鼠模型中的辐射黑色素瘤疫苗相结合：成功治疗口腔黑色素瘤和远处皮肤病变。”Cancer Gene Ther。

Hosoya Y, et al.: "Introdacusion of cytokine gene into rat neoplasm using a hand-held gene gun. II. Local bombardment of IL-12 DNA plasmid on hepatic metastases"Ann Cancer Res Ther. 8. 41-56 (2000)

Hosoya Y 等人：“使用手持基因枪将细胞因子基因引入大鼠肿瘤。II. IL-12 DNA 质粒对肝转移的局部轰击”Ann Cancer Res Ther。