Prospects for monoclonal antibody therapy of leukemia and lymphoma.

The development of monoclonal antibodies has led to renewed interest in the use of antibodies to treat malignant disease. Unfortunately, treatment with unmodified antibodies has been disappointing. Therapy with unmodified antibodies has been limited by the failure of host effector mechanisms to eliminate antibody-coated tumor cells and by the emergence of variant cells lacking the target antigen. The use of antibodies as carriers of radionuclides has the potential for overcoming both these limitations because the conjugates will be directly cytotoxic and a conjugate bound to a cell surface will deliver radiation to adjacent cells lacking the target antigen. Experimental and clinical therapy trials of radionuclide antibody conjugates have yielded promising results with both tumor-specific antibody and with antibodies against differentiation antigens. Bone marrow toxicity has been dose limiting. Bone marrow support will most likely be required for the treatment of leukemia and lymphoma due to the marrow involvement with malignant cells. In the case of solid tumors, bone marrow infusion may allow administration of curative doses of radionuclide conjugates. Although at an early stage in development, radiolabeled antibodies have the potential for contributing significantly to the therapy of malignant disease.