LIPOPHILIC PROBES FOR TUMOR CELL SURFACES

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It has been known for some time that the lipid composition of the plasma membranes of many neoplastic cells differs from the composition of their normal counterparts. However, few attempts have been made to exploit this difference for diagnostic and therapeutic purposes. It is the main objective of this proposal to determine if the lipophilic, anionic dye, merocyanine 540 (MC 540), can be employed to both identify and selectively destroy leukemic cells. Flow cytometric analyses of MC 540 stained blood samples from leukemia patients undergoing chemotherapy or bone marrow transplantation will be performed to test the dye's potential as a diagnostic agent. Two animal models of human acute myelogenous leukemia, drug-resistant mutant cell lines and in vitro clonal cultures of normal and leukemic human hematopoietic stem cells will be used to assess the dye's ppotential as a means for the purging of residual tumor cells from autologous remission marrow grafts. Attempts to elucidate some aspects of the molecular mechanisms that underlie dye-mediated photosensitization will be based on a combined light microscopic, electron microscopic, biochemical and biological analysis of photosensitized cells. Analogs of MC 540 will be employed to define the structural requirements of the staining reaction and the photosensitization process. The proposed work could lead to an earlier detection of leukemic relapse and thus to useful individualizations of treatment. MC 540-mediated photosensitization may find an application in the in vitro purging of residual tumor cells from autologous remission bone marrow grafts.