TARGETED CELLULAR CYTOTOXICITY

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1. A murine mammary carcinoma model has been used to test the ability of targeted syngeneic T cells to eradicate transplanted solid tumor lung metastases. When given to tumor bearing mice, a genetically engineered bispecific antibody retards the growth of tumors and prolongs survival of mice. 2. A genetically engineered single chain bispecific molecule has been produced in mammalian cells and in bacteria which specifically redirects mouse T cells to lyse target cells in vitro, at ng/ml levels. 3. CD44 becomes a cytotoxic triggering molecule on human NK cells after 24 hr stimulation with IL-2 or IL-12. CD44-dependent lysis involves both serine-threonine and tyrosine kinases, and activation of CD44 is accompanied by its binding to other proteins, including one that is tyrosine phosphorylated. Similar studies have shown that CD69 becomes a cytotoxic triggering molecule on subsets of PBL after 4 days activation.