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The anti-CD19 (HD37-dgRTA) immunotoxin (IT) is a murine IgG1 monoclonal antibody conjugated to a deglycosylated ricin A chain (dgRTA). This IT is effective in selectively killing B-lineage leukemia cells obtained from children with leukemia. It is also effective in prolonging the survival and curing severe combined immunodeficient mice (SCID) mice injected with the NALM-6-UM-1 human pre-B acute lymphoblastic leukemia (ALL) cell line. The purpose of this study was to identify effective combinations of HD37-dgRTA with chemotherapy agents. To evaluate the efficacy of this IT in combination with chemotherapy, we performed in vitro and in vivo experiments combining the IT with two chemotherapy agents commonly used in the treatment of childhood ALL. The in vitro cytotoxicity assays demonstrate that the combination of HD37-dgRTA with daunorubicin or with vincristine is synergistic. The in vivo experiments show that mice treated with HD37-dgRTA had improved survival when compared to the chemotherapy agents. The mean survival for mice treated with HD37-dgRTA was 90.7 days vs 91.8 days for those receiving HD37-dgRTA plus daunorubicin. Mice that were treated with HD37-dgRTA plus vincristine survived a mean of 147.1 days. Most strikingly, 80% of the mice treated with combination of HD37-dgRTA and vincristine were long term survivors. The disease burden in each of 8 organs was also determined for the different treatment groups by polymerase chain reaction (PCR) analysis. None of the mice treated with the combination of HD37-dgRTA plus vincristine had evidence of residual disease.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]