Clinical translation of a PD-L1 PET tracer to optimize immune checkpoint therapy in patients with non-small cell lung cancers

PD-L1 PET 示踪剂的临床转化优化非小细胞肺癌患者的免疫检查点治疗

基本信息

  • 批准号:
    10418064
  • 负责人:
  • 金额:
    $ 62.48万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-06-14 至 2027-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary. Despite the efficacious application of immune checkpoint therapy (ICT) across a broad range of cancers, only a subset of patients experience remarkable clinical responses and survival. The challenge facing clinicians and researchers alike is how to deliver the most effective and timely immunotherapy to patients. From clinical trial data it is becoming increasingly evident that a single biomarker is unlikely to capture the scope and breadth of clinical responses to ICT. Rather, incorporation of multiple biomarker panels, including both pharmacodynamic and predictive biomarkers, has become a necessity. However, the number of tests that can be performed with baseline and on-treatment biopsies is limited by the amount of biopsy tissue, and has several shortcomings including inter- and intra-tumoral heterogeneity and sampling errors. Those problems are compounded in patients with metastatic disease and difficult-to-access locations. Imaging methods such as positron emission tomography (PET) enable repetitive evaluation of the whole body and facilitate real-time quantification of pharmacodynamic effects. Also, in recent years on-demand kit formulations of radiopharmaceutical preparations have enabled widespread and routine clinical use of PET in cancer care. However, PET is underutilized in guiding ICT due to the limited access to molecularly targeted radiotracers that accurately report on the activity of the immune infiltrate. Generator-produced Gallium-68-labeled radiopharmaceuticals, in kit formulation or otherwise, are increasingly used in the US and across the globe as theranostic tools for cancer but have not been reported with a focus on advancing ICT. Our project addresses the need for non-invasive biomarkers for guiding ICT with an objective to develop, translate and disseminate a radiopharmaceutical for measuring programmed death ligand 1 (PDL1). We will develop a peptide-based Gallium-68-labeled radiopharmaceutical for measuring PDL1 levels to guide ICT and conduct a first-in-human study in cancer patients. Moreover, we will create a single vial kit formulation of that agent to enable convenient radiopharmaceutical preparation and dissemination. Our radiotracer is peptide-derived and uniquely capable of measuring pharmacodynamic effects of any PD(L)-1 therapeutic in situ in 60 min. We expect that the proposed approach will be a valuable addition to ICT, especially as a non-invasive biomarker. The results generated will enable a fundamental advance in clinical management of patients undergoing ICT and carried out in close partnership with industry with an eye towards dissemination and broad access.
项目摘要。 尽管免疫检查点疗法(ICT)在广泛的癌症中得到了有效的应用,但只有 部分患者经历了显著的临床反应和生存。临床医生和医生面临的挑战 研究人员一致认为,如何为患者提供最有效和最及时的免疫治疗。来自临床试验 数据越来越明显的是,单一的生物标志物不太可能反映出 对信息通信技术的临床反应。相反,多个生物标记物小组的结合,包括药效学 和预测性生物标记物,已经成为一种必需品。但是,可以使用执行的测试的数量 基线和治疗中的活组织检查受到活组织数量的限制,有几个缺点。 包括肿瘤间和瘤内的异质性和抽样误差。这些问题在以下方面更加复杂 转移性疾病和难以接近的位置的患者。正电子发射等成像方法 断层扫描(PET)能够对全身进行重复评估,并便于实时量化 药效学效应。此外,近年来放射性药物制剂的按需试剂盒配方 使PET在癌症治疗中的广泛和常规临床应用成为可能。然而,PET在引导方面没有得到充分的利用 ICT由于获得分子靶向放射性示踪剂的机会有限,这些示踪剂准确地报告了 免疫渗透。试剂盒配方或其他形式的发电机生产的镓-68标记放射性药物, 在美国和全球范围内越来越多地被用作治疗癌症的治疗工具,但尚未有报道 重点是推进信息和通信技术。我们的项目解决了对非侵入性生物标记物的需求,用于指导ICT 目的开发、翻译和传播一种用于测量程序性死亡的放射性药物 配体1(PDL1)。我们将开发一种基于多肽的镓-68标记的用于测量PDL1的放射性药物 以指导信息和通信技术,并在癌症患者中进行首例人体研究。此外,我们将创建一个单独的小瓶 该试剂的成套配方,以便于放射性药物的制备和传播。我们的 放射性示踪剂是多肽衍生的,唯一能够测量任何PD(L)-1的药效学效应 60min内就位治疗。我们期望拟议的办法将是对信息和通信技术的宝贵补充,特别是 作为一种非侵入性生物标志物。所产生的结果将使临床管理得到根本性的进步 对接受ICT治疗的患者进行评估,并与产业界密切合作,着眼于传播 和广泛的通行证。

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 }}

Sridhar Nimmagadda其他文献

Sridhar Nimmagadda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('Sridhar Nimmagadda', 18)}}的其他基金

Clinical translation of a PD-L1 PET tracer to optimize immune checkpoint therapy in patients with non-small cell lung cancers
PD-L1 PET 示踪剂的临床转化优化非小细胞肺癌患者的免疫检查点治疗
  • 批准号:
    10645063
  • 财政年份:
    2022
  • 资助金额:
    $ 62.48万
  • 项目类别:
Non-invasive Quantification of Dose-Exposure-Response of PD-L1 Therapeutics at the Tumor
PD-L1 治疗药物对肿瘤的剂量-暴露-反应的无创定量
  • 批准号:
    9977986
  • 财政年份:
    2018
  • 资助金额:
    $ 62.48万
  • 项目类别:
Non-invasive Quantification of Dose-Exposure-Response of PD-L1 Therapeutics at the Tumor
PD-L1 治疗药物对肿瘤的剂量-暴露-反应的无创定量
  • 批准号:
    9604512
  • 财政年份:
    2018
  • 资助金额:
    $ 62.48万
  • 项目类别:
Non-invasive Quantification of Dose-Exposure-Response of PD-L1 Therapeutics at the Tumor
PD-L1 治疗药物对肿瘤的剂量-暴露-反应的无创定量
  • 批准号:
    10447016
  • 财政年份:
    2018
  • 资助金额:
    $ 62.48万
  • 项目类别:
Non-invasive Quantification of Dose-Exposure-Response of PD-L1 Therapeutics at the Tumor
PD-L1 治疗药物对肿瘤的剂量-暴露-反应的无创定量
  • 批准号:
    10197853
  • 财政年份:
    2018
  • 资助金额:
    $ 62.48万
  • 项目类别:
Imaging and targeting metastatic disease
成像和靶向转移性疾病
  • 批准号:
    8532859
  • 财政年份:
    2012
  • 资助金额:
    $ 62.48万
  • 项目类别:
Imaging and targeting metastatic disease
成像和靶向转移性疾病
  • 批准号:
    8680187
  • 财政年份:
    2012
  • 资助金额:
    $ 62.48万
  • 项目类别:

相似海外基金

Construction of affinity sensors using high-speed oscillation of nanomaterials
利用纳米材料高速振荡构建亲和传感器
  • 批准号:
    23H01982
  • 财政年份:
    2023
  • 资助金额:
    $ 62.48万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Affinity evaluation for development of polymer nanocomposites with high thermal conductivity and interfacial molecular design
高导热率聚合物纳米复合材料开发和界面分子设计的亲和力评估
  • 批准号:
    23KJ0116
  • 财政年份:
    2023
  • 资助金额:
    $ 62.48万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Development of High-Affinity and Selective Ligands as a Pharmacological Tool for the Dopamine D4 Receptor (D4R) Subtype Variants
开发高亲和力和选择性配体作为多巴胺 D4 受体 (D4R) 亚型变体的药理学工具
  • 批准号:
    10682794
  • 财政年份:
    2023
  • 资助金额:
    $ 62.48万
  • 项目类别:
Platform for the High Throughput Generation and Validation of Affinity Reagents
用于高通量生成和亲和试剂验证的平台
  • 批准号:
    10598276
  • 财政年份:
    2023
  • 资助金额:
    $ 62.48万
  • 项目类别:
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
  • 批准号:
    2233343
  • 财政年份:
    2023
  • 资助金额:
    $ 62.48万
  • 项目类别:
    Standard Grant
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
  • 批准号:
    2233342
  • 财政年份:
    2023
  • 资助金额:
    $ 62.48万
  • 项目类别:
    Standard Grant
Molecular mechanisms underlying high-affinity and isotype switched antibody responses
高亲和力和同种型转换抗体反应的分子机制
  • 批准号:
    479363
  • 财政年份:
    2023
  • 资助金额:
    $ 62.48万
  • 项目类别:
    Operating Grants
Deconstructed T cell antigen recognition: Separation of affinity from bond lifetime
解构 T 细胞抗原识别:亲和力与键寿命的分离
  • 批准号:
    10681989
  • 财政年份:
    2023
  • 资助金额:
    $ 62.48万
  • 项目类别:
CAREER: Engineered Affinity-Based Biomaterials for Harnessing the Stem Cell Secretome
职业:基于亲和力的工程生物材料用于利用干细胞分泌组
  • 批准号:
    2237240
  • 财政年份:
    2023
  • 资助金额:
    $ 62.48万
  • 项目类别:
    Continuing Grant
ADVANCE Partnership: Leveraging Intersectionality and Engineering Affinity groups in Industrial Engineering and Operations Research (LINEAGE)
ADVANCE 合作伙伴关系:利用工业工程和运筹学 (LINEAGE) 领域的交叉性和工程亲和力团体
  • 批准号:
    2305592
  • 财政年份:
    2023
  • 资助金额:
    $ 62.48万
  • 项目类别:
    Continuing Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了