Bispecific antibody pretargeted immunoPET of prostate cancer

描述（由申请人提供）：本I期申请正在提交，主要目的是开发一种基于双特异性抗体（bsMAb）预靶向程序的前列腺癌高灵敏度和特异性成像方法。该成像系统的关键特征是使用独特的重组人源化三Fab bsMAb，其具有与肿瘤相关抗原TR 0 P-2的二价结合，以及与新型半抗原HSG（组胺-琥珀酰-甘氨酸）反应的另一种单价结合Fab。它将与小分子量半抗原肽（HP）结合使用，该半抗原肽将根据Immunomedics科学家发明的一种新的快速标记肽的方法用18F进行放射性标记。这种预靶向方法已经显示出比18F-FDG在靶向癌症方面更高的灵敏度和特异性。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TF 12的bsMAb，用于通过免疫PET成像检测前列腺癌。该项目涉及TF 12的生产，TF 12将用于评估bsMAb的稳定性、免疫组织学和猴毒理学/PK研究。本项目中使用的半抗原肽已经在GMP条件下生产，本申请无成本。在考虑IND申请之前，需要进行这些研究。 公共卫生相关性：该项目将开发一种新的和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。该程序是基于三Fab人源化重组双特异性抗体，其靶向肿瘤相关抗原，TROP-2，其在几乎所有前列腺癌标本中高度表达。bsMAb与18F标记的半抗原肽一起用于预靶向设置，使用新的程序制备标记产物。该方法已被证明比18F-FDG检测癌症更敏感和特异。

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.