Research Project
8445455
DESCRIPTION (provided by applicant): Pancreatic cancer remains one of the most lethal of cancers, due to a lack of effective early detection methods, complex and invasive surgical treatments, and early spread and metastasis. Clearly, better therapeutic approaches are needed, and in parallel, improved means for detecting and staging pancreatic cancer. Prostate stem cell antigen (PSCA), originally identified as a marker in prostate and bladder cancer, and has also been recognized as highly over expressed in pancreatic adenocarcinoma. Antibodies recognizing PSCA have demonstrated biological activity in prostate cancer and are currently in clinical evaluation for treatment of pancreatic cancer. A humanized, affinity-matured anti-PSCA engineered antibody fragment (minibody; single- chain Fv-CH3 fusion protein, 80 kDa) has been generated with rapid tumor targeting and fast blood clearance optimize for imaging applications, including immunoPET. The PSCA-specific minibody has been scaled up and produced under cGMP conditions for a pilot PET imaging study in patients with metastatic prostate cancer. The overall goal of this Fast Track STTR grant proposal is to translate PSCA-specific minibodies for clinical PET imaging of pancreatic cancer. In Phase I, humanized, affinity-matured PSCA minibody will be produced and purified, radioiodination optimized and binding to recombinant PSCA confirmed, and targeting, biodistribution, clearance, and microPET imaging will be evaluated in mice bearing human pancreatic tumor xenografts. In Phase II, starting with an existing Master Cell Bank, a cGMP production run (>350 mg) of PSCA-specific minibody will be conducted; protein will be purified, vialed and tested. Test radioiodinations withI-124 will be conducted at clinical scale, and an IND application will be prepared. These steps will set the stage for a clinical imaging study in patients with pancreatic adenocarcinoma.
