The long-term objectives of this proposal are to develop an efficient, effective, safe, convenient and economical monoclonal antibodies (MAbs) labeled with radioactive phosphate for therapy of cancers. Many chemical labeling procedures are currently used, but all these methods inactivate the antibodies to a significant extent (20 - 70 percent). The technology described in this proposal avoids this serious problem and has many advantages over the current methods.
The specific aims of this proposal, designed to achieve the objectives and demonstrate the extraordinary advantages of this technology over other procedures, are: 1) Examine the in vivo distribution of [32P]radiolabeled MAbs in athymic mice bearing human tumors; 2) Evaluate the efficacy of MAbs labeled with this new technology compared to a common chemical method in arresting tumor growth; 3) Develop reagent, production, and finished product assays and protocols in preparation for clinical trials; 4) Use the new technology to develop one additional MAb to broaden the range of cancers targeted by this new procedure from adenocarcinomas in general (colon, breast, ovarian, lung, pancreatic, prostate cancers), to malignant melanoma. This work should benefit the larger population of patients and be useful to many companies developing MAbs for the treatment and detection of cancers.
PBL has developed two potential [32P] labeled MAbs as clinical candidates for therapy of adenocarcinomas. Our novel phosphorylation technology circumvents a number of the drawbacks of conventionally radiolabeled MAb therapy. The extensive advantages of PBL's phosphorylation technology can be exploited for virtually any anticancer MAb in development, in clinical trials, or already in use, including MAbs designed to treat human melanoma.
