Science, Vol.267, No.5199, 886-891, 1995
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 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 immunoconjugate might be useful in eliminating leukemia cells in patients who have failed conventional therapy.
Keywords:ACUTE LYMPHOBLASTIC-LEUKEMIA;POKEWEED ANTIVIRAL PROTEIN;SEVERE COMBINED IMMUNODEFICIENCY;DISCRETE DEVELOPMENTAL STAGES;EXPRESS FUNCTIONAL RECEPTORS;BONE-MARROW TRANSPLANTATION;SIGNAL-TRANSDUCTION COMPLEX;LYMPHOCYTES-B;GROWTH-FACTOR;PROGENITOR CELLS