Project 3: HHLA2 as a THerapeutic Target in RCC

项目 3:HHLA2 作为 RCC 的治疗靶点

基本信息

  • 批准号:
    10705141
  • 负责人:
  • 金额:
    $ 24.18万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-09-18 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

Project 3 Summary While immune checkpoint inhibitors (ICI) have revolutionized the treatment of many cancers, including metastatic clear cell renal cell carcinoma (ccRCC), the development of agents that overcome resistance to anti-PD-1/PD-L1 based therapy represents a critical unmet need for ccRCC patients. We have shown that the B7 family member HERV-H LTR-associating 2 (HHLA2) is expressed in the majority of ccRCC and recently have discovered an inhibitory receptor (KIR3DL3) for HHLA2. Monoclonal antibodies that selectively block the HHLA2/KIRDL3 interaction, which we call the HHLA2 Inhibitory Pathway (HIP), could be an important means to enhance anti-tumor immune responses. In this proposal, we will study the expression of HHLA2 and it receptors in kidney cancer on tumor cells and immune cells and the relationship of HHLA2 and PD-L1 expression on tumors cells. Using clinically annotated specimens from clinical trials of patients with ccRCC on anti-PD-1 therapy, we will determine whether HHLA2 expression is associated with lack of response to PD-1 therapy. We will elucidate the regulatory pathways that are similar and different between HHLA2 and PD-L1 to better understand the expression of these immune checkpoints in kidney cancer and how their expression may change over the course of tumor progression and selection pressures. We will identify the optimal reagents for activating T cells and NK cells through the HHLA2:KIR3DL3 pathway in both in vitro and in vivo models. Our results will direct the selection of humanized blocking antibodies of HHLA2 Inhibitory Pathway that will move into primate toxicity and human Phase I clinical trials during year two of this grant.
项目3总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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David McDermott其他文献

David McDermott的其他文献

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{{ truncateString('David McDermott', 18)}}的其他基金

Clinical characterization of Kidney Injury Molecule-1 (KIM-1) as a Biomarker in Renal Cell Carcinoma
肾损伤分子 1 (KIM-1) 作为肾细胞癌生物标志物的临床特征
  • 批准号:
    10365631
  • 财政年份:
    2021
  • 资助金额:
    $ 24.18万
  • 项目类别:
Clinical characterization of Kidney Injury Molecule-1 (KIM-1) as a Biomarker in Renal Cell Carcinoma
肾损伤分子 1 (KIM-1) 作为肾细胞癌生物标志物的临床特征
  • 批准号:
    10541150
  • 财政年份:
    2021
  • 资助金额:
    $ 24.18万
  • 项目类别:
Development Research Project (DRP)
发展研究项目(DRP)
  • 批准号:
    10705145
  • 财政年份:
    2003
  • 资助金额:
    $ 24.18万
  • 项目类别:
DF/HCC Kidney Cancer SPORE
DF/HCC 肾癌孢子
  • 批准号:
    8517013
  • 财政年份:
    2003
  • 资助金额:
    $ 24.18万
  • 项目类别:
DF/HCC Kidney Cancer SPORE
DF/HCC 肾癌孢子
  • 批准号:
    8079686
  • 财政年份:
    2003
  • 资助金额:
    $ 24.18万
  • 项目类别:
Project 3: HHLA2 as a THerapeutic Target in RCC
项目 3:HHLA2 作为 RCC 的治疗靶点
  • 批准号:
    10206027
  • 财政年份:
    2003
  • 资助金额:
    $ 24.18万
  • 项目类别:
DF/HCC Kidney Cancer SPORE Administrative Core
DF/HCC 肾癌 SPORE 管理核心
  • 批准号:
    10206019
  • 财政年份:
    2003
  • 资助金额:
    $ 24.18万
  • 项目类别:
DF/HCC Kidney Cancer SPORE Administrative Core
DF/HCC 肾癌 SPORE 管理核心
  • 批准号:
    10705111
  • 财政年份:
    2003
  • 资助金额:
    $ 24.18万
  • 项目类别:
DF/HCC Kidney Cancer SPORE
DF/HCC 肾癌孢子
  • 批准号:
    8322749
  • 财政年份:
    2003
  • 资助金额:
    $ 24.18万
  • 项目类别:
Development Research Project (DRP)
发展研究项目(DRP)
  • 批准号:
    10206028
  • 财政年份:
    2003
  • 资助金额:
    $ 24.18万
  • 项目类别:

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