Bispecific antibody pretargeted immunoPET of prostate cancer

前列腺癌双特异性抗体预靶向免疫PET

• 批准号: 8310652
• 负责人: William A. Wegener
• 金额: $ 27.68万
• 依托单位: IMMUNOMEDICS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-19 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8310652
• 关键词: 90Y; Affinity; Aluminum; Antibodies; Antigens; Area; Binding; Bispecific Antibodies; Budgets; CEACAM5 gene; Complex; Cyclic GMP; Data; Detection; Docking; Dose; Drug Formulations; Epithelial; Excision; Funding; Future; GMP lots; Generations; Glycine; Glycoproteins; Goals; Haptens; Histamine; Human; Image; Imaging Techniques; Immunoglobulin G; Label; Legal patent; Malignant Neoplasms; Malignant neoplasm of prostate; Methods; Molecular Weight; Monkeys; Names; Normal tissue morphology; Nude Mice; Parents; Peptides; Pharmaceutical Preparations; Phase; Positron-Emission Tomography; Preclinical Testing; Preparation; Procedures; Product Labeling; Prostate; Publishing; Radiolabeled; Radionuclide Imaging; Recombinants; Reporting; Research; SN-38; Scientist; Secure; Specimen; Staining method; Stains; System; TACSTD2 gene; Technology; Testing; Tissues; Toxicology; Transducers; Tumor Antigens; Virus; Xenograft procedure; base; cost; experience; human TACSTD1 protein; human TACSTD2 protein; human tissue; imaging modality; improved; manufacturing process; novel; preclinical study; radiotracer; rapid technique; research clinical testing; tumor

DESCRIPTION (provided by applicant): This Phase I application is being submitted with the main objective to develop a highly sensitive and specific imaging method for prostate cancer that is based on a bispecific antibody (bsMAb) pretargeting procedure. The key features of this imaging system is the use of a unique recombinant, humanized tri-Fab bsMAb with divalent binding to the tumor-associated antigen, TROP-2, and another monovalent-binding Fab reactive with the novel hapten, HSG (histamine- succinyl-glycine). It will be used in combination with a small molecular weight hapten-peptide (HP) that will be radiolabeled with 18F based on a new, rapid method for labeling peptides invented by Immunomedics scientists. This pretargeting method has already been shown to be highly sensitive and more specific in targeting cancer than 18F-FDG. Immunohistology studies have shown TROP-2 is widely expressed in all forms of prostate cancer, primary and metastatic, and thus we plan to develop the bsMAb known as TF12 for detecting prostate cancer by ImmunoPET imaging. The project involves the manufacturing of TF12 that will be used to assess bsMAb stability, immunohistology, and toxicology/PK studies in monkeys. The hapten-peptide to be used in this project is already being produced under GMP conditions at no cost to this application. These studies are required before a IND application can be considered. PUBLIC HEALTH RELEVANCE: This project will develop a new and promising positron-emission tomography (PET) imaging system for the detection of prostate cancer. The procedure is based on a tri-Fab humanized recombinant bispecific antibody that targets the tumor-associated antigen, TROP-2 that is highly expressed in nearly all prostate cancer specimens. The bsMAb is used in a pretargeting setting with an 18F-labeled hapten-peptide using a novel procedure for preparing the labeled product. This procedure has been shown to be more sensitive and specific than 18F-FDG for detecting cancer.

描述（由申请人提供）：提交此一期申请的主要目的是开发一种基于双特异性抗体 (bsMAb) 预靶向程序的高度灵敏和特异性的前列腺癌成像方法。该成像系统的关键特征是使用独特的重组、人源化三 Fab bsMAb，其二价结合至肿瘤相关抗原 TROP-2，以及另一种单价结合 Fab 与新型半抗原 HSG（组胺-琥珀酰-甘氨酸）发生反应。它将与小分子量半抗原肽 (HP) 结合使用，该肽将根据免疫医学科学家发明的一种新的、快速的肽标记方法，用 18F 进行放射性标记。这种预靶向方法已被证明比 18F-FDG 在靶向癌症方面具有更高的敏感性和特异性。免疫组织学研究表明 TROP-2 在所有形式的前列腺癌（原发性和转移性）中广泛表达，因此我们计划开发称为 TF12 的 bsMAb，用于通过免疫 PET 成像检测前列腺癌。该项目涉及 TF12 的生产，该 TF12 将用于评估 bsMAb 稳定性、免疫组织学和猴子毒理学/药代动力学研究。该项目中使用的半抗原肽已在 GMP 条件下生产，且该应用无需支付任何费用。在考虑 IND 申请之前需要进行这些研究。 公共健康相关性：该项目将开发一种新的、有前途的正电子发射断层扫描（PET）成像系统，用于检测前列腺癌。该程序基于 tri-Fab 人源化重组双特异性抗体，该抗体针对肿瘤相关抗原 TROP-2，TROP-2 在几乎所有前列腺癌标本中都高度表达。 bsMAb 与 18F 标记的半抗原肽一起用于预靶向环境，并采用一种制备标记产品的新颖程序。事实证明，该方法在检测癌症方面比 18F-FDG 更灵敏、更特异。