TARGETED CELLULAR CYTOTOXICITY

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1.Human PBL that are targeted with bispecific antibodies exhibit an antitumor activity mediated by cytokines secreted into the medium as a result of T cell receptor crosslinking. This activity is different from targeted cytolysis as measured by 5lCr release in that it leads to the eradication of both target and bystander tumor cells. Two cytokines involved in blocking tumor growth are TNF-alpha and IFN-gamma. Induced cytokine release may be a major means by which targeted lymphocytes block tumor growth in vivo. 2. Targeted human PBL were tested for the ability to block the growth of established human ovarian carcinoma in nude mice. When given 4 days after tumor, PBL coated with anti-CD3 containing bispecific antibodies greatly decreased the number of mice bearing observable tumor at day 15, and at least doubled the long term survival times of tumor bearing mice.