The anti-tumor activity of T-cells, NK cells, and macrophages can be augmented by lymphokines and cytokines, monoclonal antibodies (Mabs) against tumor antigens, and combinations of Mabs and effector cell activators. Heteroantibodies with dual specificity were constructed by chemically cross-linking Mab against the human T-cell CD3 antigen with antibodies recognizing surface antigens on colon and ovarian tumors. Utilizing normal human peripheral blood lymphocytes, it was shown that these heteroantibodies, and in some cases, monomeric anti-tumor Mab, potentiated the killing of cultured tumor cells. In addition, heteroantibody-directed cytotoxicity was enhanced by effector cell activation with either IL-2 or anti-CD3 Mab. Thus, heteroantibodies may provide a new immunotherapeutic strategy for targeting cytotoxic immune cells to tumors.
