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Science 10 February 1995:
Vol. 267. no. 5199, pp. 886 - 891
DOI: 10.1126/science.7531365
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Articles

Science, Vol 267, Issue 5199, 886-891
Copyright © 1995 by American Association for the Advancement of Science

articles

Biotherapy of B-cell precursor leukemia by targeting genistein to CD19-associated tyrosine kinases

FM Uckun, WE Evans, CJ Forsyth, KG Waddick, LT Ahlgren, LM Chelstrom, A Burkhardt, J Bolen, and DE Myers

Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis 55455.

B-cell precursor (BCP) leukemia is the most common form of childhood cancer and the second most common form of acute leukemia in adults. Human BCP leukemia was treated in a severe combined immunodeficient mouse model by targeting of the tyrosine kinase inhibitor Genistein (Gen) to the B cell-specific receptor CD19 with the monoclonal antibody B43. The B43-Gen immunoconjugate bound with high affinity to BCP leukemia cells, selectively inhibited CD19-associated tyrosine kinases, and triggered rapid apoptotic cell death. At less than one-tenth the maximum tolerated dose more than 99.999 percent of human BCP leukemia cells were killed, which led to 100 percent long-term event-free survival from an otherwise invariably fatal leukemia. The B43-Gen immuno-conjugate might be useful in eliminating leukemia cells in patients who have failed conventional therapy.


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