The overall goal of this SBIR application is to initiate a clinical trial with a bispecific antibody (bsMAb) pretargeting procedure for detecting pancreatic carcinoma, based on a highly specific antibody (PAM4) recognizing an epitope found in pancreatic mucin. The pretargeting procedure has been shown pre-clinically and clinically to be highly sensitive and more specific than 18F-FDG for PET imaging, and recently we have developed a novel "AlF"-procedure for fluorinating peptides for immunoPET with pretargeting. Immunomedics has already completed the GMP-manufacturing of the bsMAb (TF10) and the hapten-peptide (IMP485) that will be used for this clinical study. However, prior to initiating clinical studies, Immunomedics will need to have a required PK/acute toxicity study performed in a relevant animal species (monkeys), an immunohistology study following the Points to Consider, showing the reactivity of the TF10 bsMAb with tissues, and finally some basic animal studies with the GMP-derived products to illustrate targeting conditions. We intend to complete these tasks as part of the Phase I SBIR application, and then later apply for Phase II funding to cover part of the expenses of the clinical trial.
Public Health Relevance Statement: Public Health Relevance: This project seeks to develop a bispecific antibody (bsMAb) pretargeting procedure based on the humanized PAM4 antibody that is highly specific for pancreatic cancer. Since preclinical studies have shown pretargeting can be more sensitive and specific than 18F-FDG-PET for cancer detection, we believe the specificity of the bsMAb for pancreatic carcinoma can allow this pretargeting procedure to become a highly reliable method for detecting pancreatic cancer, potentially in its early stage of development.
Project Terms: 90Y; Acute; Address; Animals; Antibodies; Applications Grants; Autopsy; base; Binding (Molecular Function); Biological Markers; Bispecific Antibodies; Blood; CA-19-9 Antigen; Cancer Detection; cancer type; Cancerous; Clinical; Clinical Research; Clinical Trials; Companions; Complement; Contracts; Detection; Development; Diagnosis; Disease; Docking; Dose; Drug Kinetics; Epitopes; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; Funding; Glycine; Goals; Grant; Half-Life; Haptens; Histamine; Human; Image; imaging modality; Immunoglobulin G; improved; Institution; interest; Investigation; Label; Legal patent; Lesion; Longevity; Lymphoma; Malignant - descriptor; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Malignant Neoplasms; Methods; molecular imaging; Monitor; Monkeys; Mucins; Normal tissue morphology; novel; oncology; Pancreas; Pancreatic carcinoma; Pancreatic Intraepithelial Neoplasia; Pancreatitis; Patients; Peptides; Phase; Positron-Emission Tomography; pre-clinical; preclinical study; Predictive Value; Preparation; Procedures; Production; public health relevance; Radioisotopes; Radiolabeled; radiotracer; Randomized; Recombinants; Reporting; research clinical testing; response; Running; Safety; Site; Small Business Innovation Research Grant; Specificity; Staging; Technology; Therapeutic; Therapeutic Uses; Time; Tissues; Toxic effect; tumor; uptake; X-Ray Computed Tomography; Xenograft Model; Xenograft procedure
