Efficacy Of An Anti-Cd138 Immunotoxin And Doxorubicin On Drug-Resistant And Drug-Sensitive Myeloma Cells

Multidrug resistance is an increasing problem in the treatment of cancer. We evaluated in vitro the effect of an anti-CD 138 plasma-cell-specific immunotoxin (IT, B-B4-SO6) in combination with the chemotherapeutic drug doxorubicin on drug-sensitive and drug-resistant variants of the multiple-myeloma (MM)-derived cell line RPM18226 and freshly isolated malignant-myeloma cells. Drug-resistant RPM18226 cells were still sensitive to the IT, although to a lesser extent than drug-sensitive cells. In the clonogenic assay, using 10 nM B-B4-SO6, at least 5 logs kill was found for drug-sensitive RPM18226 cells, vs. 2.5 logs kill for the drug-resistant RPM18226 cells. When a sub-optimal dose of I nM IT was combined with 3 ng/ml doxorubicin, which was toxic for drug-sensitive but not for drug-resistant cells, an additive effect was found for drug-sensitive RPM18226 cells. The IT did not influence the sensitivity of resistant cells for doxorubicin. We therefore speculate that this type of IT, may be of more value in combination with primary chemotherapy. The effect of B-B4-SO6 on malignant-myeloma cells of patients was investigated in a viability assay. Both drug-sensitive and drug-resistant cells from MM patients were sensitive to B-B4-SO6. After 2 days, a 50% kill of malignant cells was found when 10 nM IT were used. Doxorubicin was effective only on sensitive cells, and there was a tendency for an additive effect in the combination of these cells. Int. J, Cancer 83:571-576, 1999. (C) 1999 Wiley-Liss, Inc.