Combination of magnetic and chemocytotoxic cancer cell depletion for autologous bone marrow transplantation.
An artificial mixture of breast cancer cell line cells (T-47D) and normal human marrow cells was used to investigate optimal approaches for autologous BMT. The experiments were designed to test the applicability of chemocytotoxic agents, a dye-mediated photolytic agent and SBA for in vitro purging in autologous BMT of patients with advanced malignancies. Treatment with high concentration of etoposide (VP-16) (10 to 80 micrograms/ml) resulted in a maximal depletion of 1.5 log, whereas more efficient tumor cell eradication (2.5 log) was achieved by 30-min incubation with 100 micrograms/ml4HC. Photosensitization by exposure for 90 min to daylight in the presence of MC-540 could remove only 1 log of T-47D cells. The chemocytotoxic treatment with 4HC was chosen to follow initial tumor cell separation by SBA bound to polystyrene magnetic beads that had previously been shown to bind to several cancer cell types while sparing marrow progenitor cells. Artificial mixtures containing 10 to 14% T-47D cells in fresh normal BM cells were subjected to SBA-magnetic beads, and the SBA-negative fraction was further treated with 4HC. The combined two-step procedure resulted in a consistent tumor cell depletion of greater than 4 logs. The purging procedure appears acceptable for clinical marrow purging prior to cyropreservation and autotransplantation in patients with documented BM involvement of neoplastic cells sensitive to 4HC with positive binding to SBA such as breast cancer.
Morecki
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Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Slavin
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D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000628:therapy*; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008280:Magnetics; D008863:Microspheres; D011137:Polystyrenes; D011744:Pyrimidinones / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D011137:Polystyrenes; D011744:Pyrimidinones; D011838:Radiation-Sensitizing Agents; C003954:merocyanine dye; D005047:Etoposide; D003520:Cyclophosphamide; C011272:perfosfamide