The selective uptake of benzoporphyrin derivative mono-acid ring A results in differential cell kill of multiple myeloma cells in vitro

Stefan Glück, Antony Chadderton, Anthony D. Ho

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

High-dose chemotherapy (HDCT) and autotogous 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 BPD-MA 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, BPD-MA 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.

Original languageEnglish (US)
Pages (from-to)846-853
Number of pages8
JournalPhotochemistry and Photobiology
Volume63
Issue number6
DOIs
StatePublished - Jun 1996

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry

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