Research Project
6141577
Monoclonal antibodies (MAbs) are used for the diagnosis and therapy of cancers. However, their effectiveness in eradicating tumor cells is limited when MAbs are modified chemically to carry radioisotopes or drugs. The first MAbs prepared under this proposal will be used to target human adenocarcinoma tumor antigens. Our overall aim is to construct MAbs which can be radiolabeled with [32P]phosphate and retain the radioactive phosphate. Proteins are labeled by a simple procedure which does not denature the protein. Even proteins with no previous phosphorylation site can be engineered to incorporate multiple phosphorylation sites, to create a molecule highly effective in diagnosing and treating cancers. Molecular modeling will be used to design the optimal molecules. The phosphorylated MAb will be evaluated for its ability to bind cell surface tumor antigens and for its stability and distribution in mice. Ultimately, the MAb will be used in animals to determine the pharmacokinetics, distribution and stability of the phosphate- MAb bond in mice. The results of this project will be applicable to many monoclonal antibodies targeted to tumor antigens, and our long term objective is to develop a wide variety of radiolabeled MAbs for special diagnostic uses and for the targeted destruction of specific cancers. PROPOSED COMMERCIAL APPLICATIONS: A wide variety of phosphorylatable reagents (monoclonal antibodies, IL-2, other cytokines and growth factors), which are specific for various tumors, will be developed as antitumor molecules for targeted cancer radiotherapy. These new radiopharmaceuticals will use the isotype 32P for the first time ever for the targeted therapy of cancer.
