Monoclonal antibodies in the treatment of malignancy: Rationale for combined treatment with other biologic response modifiers

Monoclonal antibodies (MAbs) have proven valuable as adjuncts in the diagnosis and treatment of patients with malignant disease. Murine MAbs - both unmodified and conjugated with immunotoxins, radioisotopes, or cytotoxic agents - have been used to treat patients with metastatic cancer. Results of these trials have yielded only transient reponses achieved in a minority of patients. Reasons for failure are manifold, including human antimurine antibody formation, tumor antigen heterogeneity, and weak cytotoxic effects. One possible solution might be the combination of MAbs with other biologic response modifiers (BRMs) to enhancer their antitumor activity. A phase I trial of the MAb L6 in combination with subcutaneous interleukin-2 was undertaken in patients with advanced adenocarcinoma. Although antitumor activity was modest, antibody-dependent cellular cytotoxicity was enhanced by adding interleukin-2, providing incentive for continued studies combining BRMs.