The cellular basis for in vitro generation of activated killer cells against tumors has been partially established, using polyinosinic acid (Poly I) and purified recombinant IL-2 as the activating agents. Precursor cells, which include both Thy 1+ and Thy 1- cells are stimulated by IL-2 and probably by additional lymphokines produced by accessory (macrophage and/or B cells) cells and L3T4+ helper T cells. The generation of anti-tumor cytotoxic cells is inhibited in a strain-dependent fashion by accessory cells. Together, low doses of IL-2 and ancillary activating agents (e.g., Poly I) generate levels of anti-tumor activity equivalent to those generated by high doses of IL-2 alone. Human PBL, activated in vitro with IL-2 and treated with hybrid monoclonal antibodies, block growth of human colon carcinoma cells in tumor neutralization assays in nude mice. The hybrid molecules consist of cross-linked monoclonal antibodies, which react 1) with immunoglobulin Fc receptors on K cells or with the antigen receptor complex on cytotoxic T lymphocytes and 2) with human colon carcinoma cells.
