Our long term goal is to elucidate the mechanisms involved in the destruction of tumor cells by the immune system. This application focuses on the mechanisms of cytotoxicity mediated by platelets. The participation of platelets in the destruction of antibody-sensitized targets such as erythrocytes, neoplastic cells and schistosomal larvae has been appreciated only recently. We expect that the study of platelet-mediated cytotoxicity will add new information on the mechanisms of cell-mediated cytotoxicity involving the generation of cytotoxic factor(s) from the membranes and will facilitate the use of this reaction in the treatment of neoplastic diseases. The specific areas to investigate involve: (1) Obtaining additional evidence that the entire molecular assembly capable of recognizing and lysing target cells resides in the platelet plasma membrane. (2) Characterizing functionally the lesion in target membranes. (3) Studying by electron microscopy the interaction between platelets and various targts. (4) Characterizing and isolating the lytic molecule(s). (5) Identifying the molecules involved in the recognition of target cells and in the generation of the lytic molecule(s). (6) Comparing the mechanisms of erythrocyte lysis by mouse and human platelets. (7) Studying the mechanisms of platelet-mediated tumor cell lysis. (8) Exploring the use of platelets as a carrier of cytotoxic drugs or agents to enhance platelet-mediated killing of specific tumor cell targets.
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