The objective of this proposal is to develop a system for the removal of tumor cells from bone marrow using immobilized monoclonal antibodies. The capacity of this system, as well as, depletion kinetics and immunologic specificity will be determined. The antibodies will be site-specifically immobilized using proprietary chemistry. CYTOGEN's site specific immobilization chemistry involves oxidation of the oligosaccharide moieties of the antibodies which are located in the constant region of the antibody heavy chain. Coupling the substrate to the oligosaccharide should result in highly efficient immunoreactive surfaces with excellent retention of immunospecificity, thereby representing an improved method for separating the desired cell populations. Previous work in our laboratories has demonstrated the feasibility of selectively removing T cell subpopulations from flowing citrated whole human blood. Phase I research will quantitate the characteristics of a continuous flow device which will remove leukemic cells from blood. Subsequently, the immobilization chemistry will be applied using an anti-neuroblastoma antibody. In Phase II this system will be quantitated. The selective removal of neuroblastoma cells from bone marrow by virtue of the specificity of the immobilized antibody will provide treatment for this disease, and a model for removal of other tumor cells from bone marrow.
