This project is examining the role that monoclonal antibodies (MAb) against human colonic tumor antigens have in directing and augmenting the cytotoxic activity of NK/LAK cells and T cells. A MAb designated D612 (IgG2a) has been generated that uniformly reacted with the cell surface of approximately 80% of primary or metastatic colorectal carcinomas. Normal tissue reactivity of D612 was confined mainly to the small and large intestine, while non-gastrointestinal normal tissues were routinely negative. D612 mediated antibody-dependent cellular cytotoxicity in conjunction with normal human peripheral blood mononuclear cells was increased by effector cell activation with interleukin 2 (IL-2). For retargeting of T cells, heteroantibody conjugates between the anticolon tumor MAb, B38.1, and anti-CD3 (OKT-3) were chemically prepared, and these were tested along with effectors obtained from PBMNC stimulated with anti-CD3 and IL-2. The heteroantibody-mediated cellular cytotoxicity activity was similar on a per cell basis among effector populations prepared by stimulation with IL-2, anti-CD3, or a combination of these reagents. However, the total lytic activity of anti-CD3 + IL-2-stimulated cultures was much higher due to the greater expansion in cell number achieved by the combination treatment. These studies suggest that MAbs with restricted normal tissue reactivity and ability to direct the cellular cytotoxicity of a broader spectrum of killer lymphocytes activated by lymphokines and other agents might augment the efficacy of colon cancer immunotherapy.
