BIOTHERAPY OF B-CELL PRECURSOR LEUKEMIA BY TARGETING GENISTEIN TO CD19-ASSOCIATED TYROSINE KINASES

B-cell precursor (BCP) leukemia is the most common form of childhood c ancer and the second most common form of acute leukemia in adults. Hum an BCP leukemia was treated in a severe combined immunodeficient mouse model by targeting of the tyrosine kinase inhibitor Genistein (Gen) t o the B cell-specific receptor CD19 with the monoclonal antibody B43. The B43-Gen immunoconjugate bound with high affinity to BCP leukemia c ells, selectively inhibited CD19-associated tyrosine kinases, and trig gered rapid apoptotic cell death. At less than one-tenth the maximum t olerated dose more than 99.999 percent of human BCP leukemia cells wer e killed, which led to 100 percent long-term event-free survival from an otherwise invariably fatal leukemia. The B43-Gen immunoconjugate mi ght be useful in eliminating leukemia cells in patients who have faile d conventional therapy.