Aihara M, Aihara Y, Schmidt-Wolf G, Schmidt-Wolf I, Sikic B I, Blume K G, Chao N J
Department of Medicine, Stanford University School of Medicine, CA.
Blood. 1991 May 1;77(9):2079-84.
Selective removal of malignant cells (purging) from bone marrow (BM) is a concern in autologous BM transplantation (ABMT). Use of vincristine, etoposide, or doxorubicin for purging could be rendered ineffective by the presence of multidrug-resistant (MDR) tumor cells. To circumvent this particular problem, we investigated whether 17F9, a monoclonal IgG2b antibody directed against the cell surface product of the MDR gene, P-glycoprotein, is effective in selective removal of MDR cells from BM when used with rabbit complement (C'). Using two different cell lines we have demonstrated that 17F9 + C' selectively lyses MDR-positive cells. Three rounds of antibody + C' resulted in 96.4% +/- 3.6% kill of K562/DOX and 100% +/- 0% of CEM/VLB cells. Mixtures of malignant cells and normal BM resulted in 99.85% removal of K562/DOX and 99.91% removal of CEM/VLB clonogenic cells. This treatment did not affect normal committed precursors compared with C' alone. The addition of the cytotoxic agent etoposide (VP-16) following antibody purging results in a 4.6 log reduction of malignant cells. Furthermore, this antibody was effective when used against patients' leukemic blasts. These results suggest the use of 17F9 + C' is effective and selective for removal of MDR cells from BM before ABMT and the addition of VP-16 enhances the purging efficacy.
从骨髓（BM）中选择性去除恶性细胞（清除）是自体骨髓移植（ABMT）中的一个关注点。使用长春新碱、依托泊苷或阿霉素进行清除可能会因多药耐药（MDR）肿瘤细胞的存在而失效。为了解决这个特殊问题，我们研究了17F9（一种针对MDR基因细胞表面产物P-糖蛋白的单克隆IgG2b抗体）与兔补体（C'）联合使用时，是否能有效从骨髓中选择性去除MDR细胞。使用两种不同的细胞系，我们证明了17F9 + C'能选择性裂解MDR阳性细胞。三轮抗体 + C'处理导致K562/DOX细胞的杀伤率为96.4% +/- 3.6%，CEM/VLB细胞的杀伤率为100% +/- 0%。恶性细胞与正常骨髓的混合物导致K562/DOX克隆形成细胞的去除率为99.85%，CEM/VLB克隆形成细胞的去除率为99.91%。与单独使用C'相比，这种处理对正常定向祖细胞没有影响。抗体清除后添加细胞毒性药物依托泊苷（VP-16）可使恶性细胞减少4.6个对数级。此外，该抗体用于患者白血病原始细胞时也有效。这些结果表明，在ABMT前使用17F9 + C'从骨髓中有效且选择性地去除MDR细胞，添加VP-16可增强清除效果。
