The selective uptake of benzoporphyrin derivative mono-acid ring A results in differential cell kill of multiple myeloma cells in vitro.
High-dose chemotherapy (HDCT) and autologous bone marrow/blood stem cell transplantation are an effective combination for treating a number of malignant disorders. The contamination of the autograft by malignant cells may be a reason for recurrences in spite of this treatment, for instance, in multiple myeloma. Therefore, we evaluated the use of photodynamic therapy (PDT) using the photosensitizer benzoporphyrin derivative mono-acid ring A (BPD-MA) on multiple myeloma cells in comparison to the components of the normal bone marrow (NBM) and peripheral blood apheresis product. Flow cytometry was used to measure differential BPDMA uptake of NBM components: namely lymphocytes, monocytes, granulocytes and enriched hematopoietic stem cell (CD34+) populations and also the multiple myeloma cell lines OCI-MY7 and OCI-MY4. When each population was measured individually, the order of uptake was [OCI-MY7/MY4] > [CD34+] > [granulocytes] = [monocytes] >> [lymphocytes]. Further, clonogenic assay was used to demonstrate surviving fractions for OCI-MY7, OCI-MY4 and NBM in vitro. The LD90 for OCI-MY7 and OCI-MY4 was between 10 and 20 ng/mL BPD-MA whereas this concentration did not show any significant cell kill for the colony-forming units-granulocyte/macrophage (CFU-GM) and burst-forming units-erythrocyte (BFU-E). When the NBM was "contaminated" with multiple myeloma cells in vitro, the LD90 for OCI-MY7 in this cell mixture was shifted to between 40 and 80 ng/mL BPD-MA. However, at 40 ng/mL BPD-MA at least 50% of normal CFU-GM and BFU-E colonies survived. For CFU-GM and BFU-E derived from the enriched CD34+ cell population, BPDMA up to a concentration of 80 ng/mL did not significantly reduce the surviving fractions. We have observed a 3-4 log therapeutic window with differential cell kill when comparing multiple myeloma cell lines to the components of the NBM and apheresis product in vitro. We conclude, that BPD-MA is a molecule potentially useful as an ex vivo purging agent.
Glück
S
S
Northeastern Ontario Regional Cancer Centre, Sudbury, Canada.
Chadderton
A
A
Ho
A D
AD
D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D018462:Photobiology; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011166:Porphyrins / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D011166:Porphyrins; C504224:benzoporphyrin D