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）：该阶段申请是由主要目标提交的，以开发基于双特异性抗体（BSMAB）预定程序的前列腺癌的高度敏感和特定的成像方法。该成像系统的关键特征是使用独特的重组，人源化的三fab bsmab，具有与肿瘤相关的抗原，trop-2的二价结合，以及与新颖的HSG（组胺------组胺-----琥珀酰基甘氨酸）。它将与小的分子量抗肽（HP）结合使用，该肽将基于一种新的快速方法，用于标记由免疫医学科学家发明的肽标记的新方法。与18F-FDG相比，这种有限的方法已经显示出高度敏感性，在靶向癌症方面更具体。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，因此我们计划开发被称为TF12的BSMAB，用于通过免疫图成像检测前列腺癌。该项目涉及将用于评估猴子中BSMAB稳定性，免疫组织学和毒理学/PK研究的TF12的制造。该项目中使用的HAPEN肽已经在GMP条件下生产，该应用程序无需支付本应用程序。在考虑IND应用之前，需要这些研究。 公共卫生相关性：该项目将开发出一种新的且有希望的正电子发射断层扫描（PET）成像系统，用于检测前列腺癌。该方法基于三型人源化重组双特异性抗体，该抗体靶向与肿瘤相关的抗原Trop-2，该抗体在几乎所有前列腺癌标本中都高度表达。 BSMAB使用新型程序来制备标记产品的新方法，用于带有18F标记的Hapten肽的预先设置。对于检测癌症，该过程已显示出比18F-FDG更敏感和特异性。