INTRATIBIAL INJECTION OF AN ANTI-DOXORUBICIN MONOCLONAL-ANTIBODY PREVENTS DRUG-INDUCED MYELOTOXICITY IN MICE

With few exceptions, the major limit to high-dose chemotherapeutic tre atments is the severity and duration of drug-induced myelosuppression. We have recently developed a monoclonal antibody, MAD11, which reacts with the potent anti-tumour antibiotic doxorubicin and other anthracy clines. To protect directly pluripotent stem cells and cells of the ha ematopoietic microenvironment in the bone marrow against doxorubicin c ytotoxicity, the monoclonal antibody MAD11 was injected into the tibia l bone of mice before chemotherapeutic treatment. All mice pretreated intratibially with MAD11 and injected with 14 mg kg-l body weight of d oxorubicin survived, whereas 41% of mice treated with doxorubicin alon e died. At a higher dose of doxorubicin (18 mg kg(-1)), early mortalit y (first 6 days) was similar in the groups, but no deaths were observe d thereafter in the intratibially MAD11-treated group, whereas most of the mice treated with doxorubicin alone died. Data obtained in mice i njected with P388 leukaemia cells showed that the intratibial injectio n of MAD11 did not compromise the anti-tumoral activity of doxorubicin . Moreover, the administration of the anti-doxorubicin monoclonal anti body before chemotherapeutic treatment effectively reduced apoptosis i nduced by doxorubicin in the bone marrow cells. These data suggest the usefulness of monoclonal antibodies against chemotherapeutic drugs in the local protection of bone marrow without influencing the anti-tumo ur properties of the drug.