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Establishment of a Human t(4;11) Leukemia in Severe Combined Immunodeficient Mice and Successful Treatment Using Anti-CD19 (B43)-Pokeweed Antiviral Protein Immunotoxin¹

Bone Marrow Transplantation Program [F. M. U., J. H. K.] and Departments of Laboratory Medicine/Pathology [B. J., W. B. J., J. H. K.], Pediatrics [F. M. U., J. H. K.], and Therapeutic Radiology [F. M. U.], University of Minnesota, Minneapolis, Minnesota 55455

Human acute leukemia, with a chromosomal translocation involving chromosomes 4 and 11, t(4;11)(q21;q23), is the most common form of leukemia in infants and responds very poorly to conventional therapy. A human CD19⁺ mixed-lineage leukemia cell line with a t(4;11)(q21;q23) translocation, RS4;11, disseminated and proliferated in the hematopoietic tissues and other organs of mice with severe combined immunodeficiency in a manner similar to that observed in humans and killed 100% of the animals. The anti-CD19(B43)-pokeweed antiviral protein immunotoxin selectively inhibited clonogenic RS4;11 cells in vitro, markedly reduced the burden of disseminated leukemia of severe combined immunodeficient mice, and, most importantly, resulted in the long-term survival of treated animals. This severe combined immunodeficient mouse model should be useful for the design of more effective treatment strategies for refractory human leukemias.

¹ This work was supported by Grants CA49721, CA21737, and CA51425 from the National Cancer Institute/NIH and the Childrens Cancer Research Fund. J. H. K. is the recipient of an Outstanding Investigator Award (CA49721) from the National Cancer Institute. F. M. U. is a Scholar of the Leukemia Society of America.

² To whom requests for reprints should be addressed, at University of Minnesota, Department of Pediatrics, Box 86 UMHC, 420 Delaware Street, Minneapolis, MN 55455.

Received 7/18/91. Accepted 11/ 1/91.

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