Lentiviral Vectors for TCR Immunotherapy Targeted to HCV

用于针对 HCV 的 TCR 免疫治疗的慢病毒载体

基本信息

  • 批准号:
    7224649
  • 负责人:
  • 金额:
    $ 28.97万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2007
  • 资助国家:
    美国
  • 起止时间:
    2007-04-15 至 2008-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this proposal is to evaluate the novel concept whether using lentiviral-engineered T cells that express T cell receptor (TCR) capable of recognizing hepatitis C (HCV)-induced liver tumor cells will improve efficacy of immunotherapy for this disease. Chronic infection with HCV can lead to several liver diseases including hepatocellular carcinoma and cirrhosis. These liver diseases are the major indication for liver transplantation. IFN-? in combination with ribavirin is used to treat HCV infections with limited success. In order to reduce the worldwide morbidity and mortality from HCV infection and HCV related diseases more effective treatments for HCV infected patients are necessary. In this proposal we will test the fundamental hypothesis that human T cells with redirected specificity for HCV associated liver tumor cells can be created by using lentiviral vector technology and can offer a clinically relevant and successful therapeutic approach. The ultimate goal is the development of a novel and improved therapy for hepatitis HCV related malignancy, a potentially major public health concerns with approximately 3% of the world's population. Lentiviral vectors (LVs) have been successfully evaluated in Phase l clinical trials in patients with HIV/AIDS, offering the possibility to more broadly apply this technology for the treatment of other diseases, including chronic infections and cancer. Lentigen's collaborator Dr. Michael Nishimura has helped pioneer adoptive immunotherapy as a potential therapeutic approach for hepatitis. Therefore, in Aim 1 of this proposal we will develop self inactivating (SIN) LVs expressing a and ¿ chains of the TCR capable of recognizing the HCV and/or liver tumor cells. In Aim 2, together with Dr. Nishimura's team, we will test safety and efficacy of LVTCR transduced T cells in preventing HCV- induced liver tumor growth and treating established tumors in vivo. In summary, Lentigen Corp. and Dr. Nishimura's laboratory are uniquely positioned to provide the first comprehensive evaluation of the redirected T cell approach to generate anti-HCV induced liver tumor effects in patients infected with HCV and to apply this in a future clinical trial for patients with this life threatening disease.
描述(由申请人提供):这项建议的总体目标是评估使用表达T细胞受体(TCR)的慢病毒工程T细胞是否能够识别丙型肝炎(HCV)诱导的肝肿瘤细胞,从而提高这种疾病的免疫治疗效果。慢性感染丙型肝炎病毒可导致几种肝脏疾病,包括肝细胞癌和肝硬变。这些肝病是肝移植的主要适应症。干扰素-?与利巴韦林联合使用治疗丙型肝炎病毒感染,但效果有限。为了降低世界范围内丙型肝炎病毒感染及相关疾病的发病率和死亡率,有必要对丙型肝炎病毒感染者进行更有效的治疗。在这项建议中,我们将检验这一基本假设,即利用慢病毒载体技术可以建立对丙型肝炎病毒相关的肝肿瘤细胞具有重定向特异性的人T细胞,并可以提供一种临床相关的成功治疗方法。最终目标是开发一种新的和改进的治疗丙型肝炎相关恶性肿瘤的方法,这是一种潜在的重大公共卫生问题,约占世界人口的3%。慢病毒载体(LV)已在艾滋病毒/艾滋病患者的L期临床试验中成功进行评估,这为将这项技术更广泛地应用于其他疾病的治疗提供了可能性,包括慢性感染和癌症。Lentigen的合作者Michael Nishimura博士帮助开创了过继免疫疗法作为肝炎潜在治疗方法的先河。因此,在这项建议的目标1中,我们将开发表达TCRα链和?链的自失活(SIN)LV,能够识别丙型肝炎病毒和/或肝肿瘤细胞。在目标2中,我们将与西村博士的团队一起,在体内测试LVTCR转导的T细胞在防止丙型肝炎病毒诱导的肝肿瘤生长和治疗已建立的肿瘤方面的安全性和有效性。总之,Lentigen公司和西村博士的实验室处于独特的地位,可以对重定向T细胞方法进行首次全面评估,以在感染丙型肝炎病毒的患者中产生抗丙型肝炎病毒诱导的肝肿瘤效应,并将其应用于未来对这种威胁生命的疾病患者的临床试验。

项目成果

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Boro Dropulic其他文献

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{{ truncateString('Boro Dropulic', 18)}}的其他基金

A Novel Method of Generating Hepatitis C Virus-Like Particles using Lentivirus
利用慢病毒产生丙型肝炎病毒样颗粒的新方法
  • 批准号:
    7748047
  • 财政年份:
    2009
  • 资助金额:
    $ 28.97万
  • 项目类别:
Lentiviral expressed growth factors as a novel therapy in wound healing
慢病毒表达生长因子作为伤口愈合的新疗法
  • 批准号:
    7481788
  • 财政年份:
    2008
  • 资助金额:
    $ 28.97万
  • 项目类别:
T cell receptor gene vectors for EBV disease
EBV疾病T细胞受体基因载体
  • 批准号:
    7327262
  • 财政年份:
    2007
  • 资助金额:
    $ 28.97万
  • 项目类别:
Immunotherapy of CLL with lentiviral expressed CD40-ligand
使用慢病毒表达的 CD40 配体进行 CLL 免疫治疗
  • 批准号:
    7161658
  • 财政年份:
    2006
  • 资助金额:
    $ 28.97万
  • 项目类别:
Clinical Vector for TCR Immunotherapy Targeted to Melanoma
针对黑色素瘤的 TCR 免疫治疗的临床载体
  • 批准号:
    7914960
  • 财政年份:
    2006
  • 资助金额:
    $ 28.97万
  • 项目类别:
Clinical Vector for TCR Immunotherapy Targeted to Melanoma
针对黑色素瘤的 TCR 免疫治疗的临床载体
  • 批准号:
    8092817
  • 财政年份:
    2006
  • 资助金额:
    $ 28.97万
  • 项目类别:
Lentiviral Vectors for TCR Immunotherapy Targeted to melanoma
用于针对黑色素瘤的 TCR 免疫治疗的慢病毒载体
  • 批准号:
    7224655
  • 财政年份:
    2006
  • 资助金额:
    $ 28.97万
  • 项目类别:
Clinical Vector for TCR Immunotherapy Targeted to Melanoma
针对黑色素瘤的 TCR 免疫治疗的临床载体
  • 批准号:
    8296053
  • 财政年份:
    2006
  • 资助金额:
    $ 28.97万
  • 项目类别:
Lentiviral engineered T cell immunotherapy in tumors overexpressing mesothelin
慢病毒工程 T 细胞免疫治疗过度表达间皮素的肿瘤
  • 批准号:
    7161656
  • 财政年份:
    2006
  • 资助金额:
    $ 28.97万
  • 项目类别:
cGMP and cGLP Lentiviral Vetors
cGMP 和 cGLP 慢病毒载体
  • 批准号:
    6998379
  • 财政年份:
    2005
  • 资助金额:
    $ 28.97万
  • 项目类别:

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