Glück S, Chadderton A, Ho A D
Northeastern Ontario Regional Cancer Centre, Sudbury, Canada.
Photochem Photobiol. 1996 Jun;63(6):846-53. doi: 10.1111/j.1751-1097.1996.tb09641.x.
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.
大剂量化疗（HDCT）和自体骨髓/血液干细胞移植是治疗多种恶性疾病的有效组合。尽管采用了这种治疗方法，但自体移植物被恶性细胞污染可能是复发的原因，例如在多发性骨髓瘤中。因此，我们评估了使用光敏剂苯并卟啉衍生物单酸环A（BPD-MA）的光动力疗法（PDT）对多发性骨髓瘤细胞的作用，并与正常骨髓（NBM）和外周血单采产品的成分进行比较。采用流式细胞术测量NBM成分对BPD-MA的摄取差异：即淋巴细胞、单核细胞、粒细胞和富集的造血干细胞（CD34+）群体，以及多发性骨髓瘤细胞系OCI-MY7和OCI-MY4。当分别测量每个群体时，摄取顺序为[OCI-MY7/MY4]>[CD34+]>[粒细胞]=[单核细胞]>>[淋巴细胞]。此外，采用克隆形成试验来证明OCI-MY7、OCI-MY4和NBM在体外的存活分数。OCI-MY7和OCI-MY4的LD90在10至20 ng/mL BPD-MA之间，而该浓度对集落形成单位-粒细胞/巨噬细胞（CFU-GM）和爆式红系集落形成单位（BFU-E）未显示出任何显著的细胞杀伤作用。当NBM在体外被多发性骨髓瘤细胞“污染”时，该细胞混合物中OCI-MY7的LD90转移至40至80 ng/mL BPD-MA之间。然而，在40 ng/mL BPD-MA时，至少50%的正常CFU-GM和BFU-E集落存活。对于源自富集的CD34+细胞群体的CFU-GM和BFU-E，浓度高达80 ng/mL的BPD-MA并未显著降低存活分数。在体外将多发性骨髓瘤细胞系与NBM和单采产品的成分进行比较时，我们观察到了具有差异细胞杀伤作用的3至4个对数治疗窗口。我们得出结论，BPD-MA是一种潜在可用作体外净化剂的分子。
