The objective of this proposal is to develop techniques for using monoclonal antibodies labeled with 212Bismuth, an alpha particle emitting radionuclide, as in vitro or in vivo cytotoxic agents. Antibody conjugates developed by CYTOGEN for radioimaging localize to the tumor site only, with minimal uptake by the reticuloendothelial system, making them ideal agents for immunotherapy. CYTOGEN's proprietary, site-specific covalent attachment of chelators to the oligosacharides in the constant region, away from the antibody's binding site, yields homogeneous conjugates which retain their antigen binding activity and affinity. These chemical techniques are an improvement over existing methods for antibody modification. 212Bismuth, produced from generators obtained from the Argonne National Laboratories, has been chelated by DTPA covalently attached to monoclonal anti-tumor antibodies by the above methods. In Phase I the proposed research will demonstrate immunospecific killing of tumor cells in vitro and stability of the MAb-DTPA-212Bi conjugate in vivo. In Phase II radioimmunotherapy will be achieved in an in vivo murine tumor model. Antibody localization will be studied and therapeutic effect will be assessed. The ultimate goal of radioimmunotherapy is the treatment of humans for cancer.
