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重要窗口 细胞培养系统中的表达,以及转基因细胞或动物中基因表达的体内测量。报告基因方法在临床环境中也变得越来越重要,用于监测治疗基因的表达并在癌症的基因治疗或免疫治疗中跟踪基因修饰的免疫效应细胞。当前报告基因成像系统向临床环境的转化受到外源基因的潜在免疫原性、生物活性报告蛋白的毒性、检测灵敏度和背景信号问题的限制。我们建议开发一种内源性人类蛋白——癌胚抗原(CEA)作为 PET 报告基因,用于人类应用,例如追踪转基因 T 细胞。 CEA 应该是非免疫原性的,因为它是人类自身抗原。内源组织表达在正常成人中非常有限,并且在免疫细胞(包括 B 和 T 淋巴细胞)中不存在。我们开发了两种新型 CEA 特异性 PET 示踪剂 - 基因工程抗体片段,称为“微型抗体”和“双抗体” - 已通过 microPET 在小鼠模型中进行了评估,目前正在进行临床研究。 在用正电子发射体 124I 或 64Cu 进行放射性标记后,这些示踪剂在小鼠异种移植模型中达到每克注射剂量的 10-25%。 (1) 我们将构建并评估 CEA 的跨膜锚定和内化形式,以用作报告基因。天然 CEA 的这种刺激是必需的,因为 CEA 通过 GPI 连接与细胞膜相关联,并且可以释放和脱落。稳定转染的淋巴细胞系 评估抗 CEA 抗体结合和内化。 (2) CEA报告基因将使用PET同位素标记的抗CEA微型抗体和双抗体通过体内成像进行评估。初步表征将在携带稳定转染异种移植物的小鼠中进行。将开发逆转录病毒载体,并通过体内成像对小鼠原代 T 细胞的转导和监测进行评估。 (3) 基于先前通过噬菌体展示分离的 CEA 结合肽,将开发一类新的 PET 报告探针。项目结束时,将彻底探索和优化CEA PET报告基因以及抗CEA PET报告基因探针的设计和功能。该系统应该提供一种强大的、非侵入性的方法来监测基因表达和跟踪患者体内修饰的免疫细胞。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

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

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ 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:
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:
(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:
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:

相似海外基金

Development study on the implanted antigen-antibody reaction sensor for bird
禽类植入式抗原抗体反应传感器的研制
  • 批准号:
    26630165
  • 财政年份:
    2014
  • 资助金额:
    $ 16.25万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Investigation for Antigen-Antibody Reaction on Solid Surface Using Total X-ray Reflection
利用全 X 射线反射研究固体表面上的抗原抗体反应
  • 批准号:
    19760006
  • 财政年份:
    2007
  • 资助金额:
    $ 16.25万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Influence of enhanced antigenicity of renal vascular endothelium induced ischemia/reperfusion injury on the antigen antibody reaction in organ transplantation and the study of protective strategy for enhancedantigenicity
肾血管内皮抗原性增强所致缺血/再灌注损伤对器官移植抗原抗体反应的影响及增强抗原性保护策略的研究
  • 批准号:
    15591668
  • 财政年份:
    2003
  • 资助金额:
    $ 16.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Selective bacteria detection using dielectrophoretic impedance measurement combined with antigen-antibody reaction
介电泳阻抗测量结合抗原抗体反应进行选择性细菌检测
  • 批准号:
    14550421
  • 财政年份:
    2002
  • 资助金额:
    $ 16.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Signal Transduction Induced by Desmosomal Cadherin Antigen-Antibody Reaction in Bullous Formation in Pemphigus
天疱疮大疱形成过程中桥粒钙粘蛋白抗原抗体反应诱导的信号转导
  • 批准号:
    07670938
  • 财政年份:
    1995
  • 资助金额:
    $ 16.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
DEVELOPMENT OF THE INTRAOPERATIVE ESTIMATION OF THE PROXIMAL NERVE STUMP USING ANTIGEN-ANTIBODY REACTION ON THE ARTIFICIAL MEMBRANE
利用人工膜上抗原抗体反应进行近端神经残端术中估计的研究进展
  • 批准号:
    02670648
  • 财政年份:
    1990
  • 资助金额:
    $ 16.25万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Fluorescence Polarization and the Antigen-Antibody Reaction
荧光偏振和抗原抗体反应
  • 批准号:
    66B4288
  • 财政年份:
    1966
  • 资助金额:
    $ 16.25万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了