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

基本信息

  • 批准号:
    10544038
  • 负责人:
  • 金额:
    $ 71.49万
  • 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:
    2022-01-01 至 2026-12-31
  • 项目状态:
    未结题

项目摘要

Pancreatic cancer remains among the most lethal of solid tumors, due to late diagnosis and a high probability of metastatic spread. Effective new systemic treatments are needed in order to improve outcomes in patients. Targeted radionuclide therapy has demonstrated effectiveness cancer therapy, notably with the success of 177Lu- dotatate in neuroendocrine tumors including those of the pancreas. Prostate Stem Cell Antigen (PSCA) is upregulated in 60-80% of pancreatic adenocarcinomas, making it a promising target for antibody-directed therapy. An engineered antibody fragment, the A2 scFv-Fc2 DM has been specifically designed for optimized delivery of therapeutic radionucides in pancreatic cancer. It is based on a humanized, high-affinity anti-PSCA antibody, and contains Fc mutations engineered to foster rapid blood clearance via the hepatobiliary route. As a result, radiation dose to key organs/tissues (bone marrow and kidney) is minimized, enabling effective delivery of an alpha- or beta-emitting radionuclide to tumors. In Aim 1, biodistribution studies will be undertaken in mouse models, in order to confirm the expected tumor targeting and hepatic clearance. Formal dose estimations will be made for the scFv-Fc2 DM radiolabeled with either 177Lu or 225Ac for therapy. Aim 2 will explore the potential efficacy of the anti-PSCA scFv-Fc2 DM in mouse models of pancreatic cancer, including subcutaneous xenografts of human pancreatic tumor cells, a syngeneic model of KPC-PSCA tumors in huPSCA knock-in mice, and patient-derived pancreatic tumor xenograft models. The relative efficacies and toxicities of the alpha-emitter 225Ac and beta-emitter 177Lu will be analyzed in order to prepare for future clinical therapy studies. In Aim 3, clinical production and conjugation of the anti-PSCA scFv-Fc2 DM will be performed, testing conducted, and an IND filed. Finally, in Aim 4 we will conduct a first-in-human imaging study using 64Cu-DOTA-anti-PSCA scFv- Fc2 DM in patients with advanced pancreatic cancer, to evaluate the targeting, and clearance properties and potential radiation dose delivery of this novel engineered antibody fragment. Results from this clinical immunoPET study will be central to guiding future development of a radioimmunotherapy agent that can be implemented in a theranostic approach to pancreatic cancer.
胰腺癌仍然是最致命的实体肿瘤之一,由于较晚的诊断和高的可能性

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)
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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:
    10343450
  • 财政年份:
    2022
  • 资助金额:
    $ 71.49万
  • 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:
    $ 71.49万
  • 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:
    $ 71.49万
  • 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:
    $ 71.49万
  • 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:
    $ 71.49万
  • 项目类别:
Imaging Core
成像核心
  • 批准号:
    7315097
  • 财政年份:
    2007
  • 资助金额:
    $ 71.49万
  • 项目类别:
Recombinant Carcinoembronic Antigen as PET Reporter Gene
重组癌胚抗原作为 PET 报告基因
  • 批准号:
    7039880
  • 财政年份:
    2005
  • 资助金额:
    $ 71.49万
  • 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:
    $ 71.49万
  • 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:
    $ 71.49万
  • 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:
    $ 71.49万
  • 项目类别:

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