CELL MEDIATED CYTOTOXICITY

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The cellular basis for in vitro generation of mouse MHC- nonrestricted, activated killer cells against tumor cells has been further established by cell reconstitution tests. Results confirm and extend previous observations that the generation of activated killer cells in response to the nonspecific inducing agent polyinosinic acid requires accessory cells, T-helper cells (L3T4+ or Lyt2+), and cytotoxic precursor cells. This knowledge has been used 1) to generate thymic veto cells which induce selective tolerance, a possible mechanism for establishing tolerance to self, and 2) to identify and circumvent depressed in vitro generation of activated killer cells splenocytes from mice with acquired immunodeficiency disease induced by murine leukemia viruses. Normal human PBL have been activated in vitro with recombinant IL-2 and retargeted against human ovarian carcinoma cells by heteroconjugated monoclonal antibodies which crosslink immune cells via selected activation sites with the tumor cells. Retargeted effector cells are cytotoxic in vitro for ovarian carcinoma cells are block intraperitoneal growth of the tumor cells in nude mice when the mice are treated 4-6 days after tumor growth.