Tumor associated antigens are appropriate targets for radio- immunoconjugate therapy with monoclonal antibodies. Gastrointestinal adenocarcinomas are shown to be rich in glycoprotein antigens including the TAG-72 antigen. The TAG-72 antigen is a unique tumor associated antigen, which was originally defined by monoclonal antibody (MAb) B72.3. Second of these antibodies (MAb CC49) also exhibits high levels of binding to gastrointestinal tract cancers and has eight-fold greater affinity than MAb B72.3 for the TAG-72 antigen. Phase I trails using 1311 labeled or 90Yttrium conjugated MAb CC49 have been conducted using hematopoietic stem cell support to escalate dose. While absorbed doses in metastatic tumor sites of up to 3300 cGy have been observed, several obstacles to optimizing therapy have been encountered. In this project, we describe a series of studies designed to improve radio- immunotherapy with MAb CC49, which is predicted to be less immunogenic. These trails will explore diodistribution and pharmacokinetics of this construct and the possibility of multi-dose treatment strategies. Preclinical studies are planned with 47Scandium conjugated hCC49deltaCH2 to evaluate the best chalet, dose and schedule of administration in preparation for one of the proposed clinical trails. A dosimetry program will support the clinical studies in the conduct of all the clinical trails and will establish important new methods for dosimetry estimation using 47Scandium.
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