Recombinant Carcinoembronic Antigen as PET Reporter Gene

重组癌胚抗原作为 PET 报告基因

基本信息

  • 批准号:
    7039880
  • 负责人:
  • 金额:
    $ 16.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-05-01 至 2010-04-30
  • 项目状态:
    已结题

项目摘要

Reporter gene technology has provided an important window for basic investigations of gene expression in cell culture systems, and for in vivo measurement of gene expression in genetically modified cells or animals. Reporter gene approaches are gaining in importance in clinical settings as well, to monitor expression of therapeutic genes and to track genetically modified immune effector cells in gene therapy or immunotherapy of cancer. The translation of current reporter gene imaging systems into the clinical setting is limited by potential immunogenicity of foreign genes, toxicity of biologically active reporter proteins, sensitivity of detection, and background signal issues. We propose to develop an endogenous human protein, carcinoembryonic antigen (CEA) as a PET reporter gene for human applications such as tracking genetically modified T cells. CEA should be nonimmunogenic since it is human self-antigen. Endogenous tissue expression is very limited in normal adults and non-existent in immune cells, including B and T lymphocytes. We have developed two novel CEA-specific PET tracers - genetically engineered antibody fragments called the "minibody" and "diabody" - which have been evaluated in mouse models by microPET and which are currently in clinical studies. Following radiolabeling with the positron emitters 124I or 64Cu, these tracers reach 10-25 % injected dose per gram in murine xenograft models. (1) We will construct and evaluate transmembrane-anchored and internalizing forms of CEA for use as reporter genes. This motidication of native CEA is required because CEA is associated with the cell membrane via a GPI linkage, and can be released and shed. Stably transfected lymphoid cell lines will be evaluated for anti-CEA antibody binding and internalization. (2) CEA reporter genes will be evaluated by in vivo imaging using PET isotope labeled anti-CEA minibodies and diabodies. Initial characterization will be carried out in mice bearing stably transfected xenografts. Retroviral vectors will be developed and transduction and monitoring of murine primary T cells by imaging in vivo will also be evaluated. (3) A new class of PET reporter probe will be developed, based on CEA-binding peptides previously isolated by phage display. At the end of the project, design and function of the CEA PET reporter gene as well as anti-CEA PET reporter probes will be thoroughly explored and optimized. This system should provide a powerful, non-invasive method for monitoring gene expression and tracking modified immune cells in patients.
报告基因技术为基因基础研究提供了一个重要的窗口

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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Anna M Wu其他文献

Harnessing imaging tools to guide immunotherapy trials: summary from the National Cancer Institute Cancer Imaging Steering Committee workshop
利用成像工具指导免疫治疗试验:美国国家癌症研究所癌症成像指导委员会研讨会总结
  • DOI:
    10.1016/s1470-2045(22)00742-2
  • 发表时间:
    2023-03-01
  • 期刊:
  • 影响因子:
    35.900
  • 作者:
    Lalitha K Shankar;Heiko Schöder;Elad Sharon;Jedd Wolchok;Michael V Knopp;Richard L Wahl;Benjamin M Ellingson;Nathan C Hall;Martin J Yaffe;Alexander J Towbin;Michael D Farwell;Daniel Pryma;Tina Young Poussaint;Chadwick L Wright;Lawrence Schwartz;Mukesh Harisinghani;Umar Mahmood;Anna M Wu;David Leung;Elisabeth G E de Vries;Steven A Reeves
  • 通讯作者:
    Steven A Reeves
Arming antibodies: prospects and challenges for immunoconjugates
武装抗体:免疫偶联物的前景与挑战
  • DOI:
    10.1038/nbt1141
  • 发表时间:
    2005-09-07
  • 期刊:
  • 影响因子:
    41.700
  • 作者:
    Anna M Wu;Peter D Senter
  • 通讯作者:
    Peter D Senter

Anna M Wu的其他文献

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{{ truncateString('Anna M Wu', 18)}}的其他基金

Engineered anti-PSCA antibodies for immunoPET and targeted therapy of pancreatic cancer
用于免疫PET和胰腺癌靶向治疗的工程化抗PSCA抗体
  • 批准号:
    10544038
  • 财政年份:
    2022
  • 资助金额:
    $ 16.25万
  • 项目类别:
Engineered anti-PSCA antibodies for immunoPET and targeted therapy of pancreatic cancer
用于免疫PET和胰腺癌靶向治疗的工程化抗PSCA抗体
  • 批准号:
    10343450
  • 财政年份:
    2022
  • 资助金额:
    $ 16.25万
  • 项目类别:
(PQC4) Imaging CD8 T Cells In Tumor Immunotherapy By Immunopet
(PQC4) 在肿瘤免疫治疗中对 CD8 T 细胞进行成像 Immunopet
  • 批准号:
    8928583
  • 财政年份:
    2014
  • 资助金额:
    $ 16.25万
  • 项目类别:
(PQC4) Imaging CD8 T Cells In Tumor Immunotherapy By Immunopet
(PQC4) 在肿瘤免疫治疗中对 CD8 T 细胞进行成像 Immunopet
  • 批准号:
    8791842
  • 财政年份:
    2014
  • 资助金额:
    $ 16.25万
  • 项目类别:
In vivo imaging of T Cells using engineered antibodies and PET
使用工程抗体和 PET 对 T 细胞进行体内成像
  • 批准号:
    8786848
  • 财政年份:
    2014
  • 资助金额:
    $ 16.25万
  • 项目类别:
Cancer Molecular Imaging
癌症分子成像
  • 批准号:
    7944543
  • 财政年份:
    2009
  • 资助金额:
    $ 16.25万
  • 项目类别:
Imaging Core
成像核心
  • 批准号:
    7315097
  • 财政年份:
    2007
  • 资助金额:
    $ 16.25万
  • 项目类别:
Biological Modification of Quantum Dots for in vivo Imaging
用于体内成像的量子点的生物修饰
  • 批准号:
    7067899
  • 财政年份:
    2005
  • 资助金额:
    $ 16.25万
  • 项目类别:
High-avidity multimeric cancer imaging agent
高亲合力多聚体癌症显像剂
  • 批准号:
    6829532
  • 财政年份:
    2004
  • 资助金额:
    $ 16.25万
  • 项目类别:
High-avidity multimeric cancer imaging agent
高亲合力多聚体癌症显像剂
  • 批准号:
    6931073
  • 财政年份:
    2004
  • 资助金额:
    $ 16.25万
  • 项目类别:

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