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

作者：Fatih Mehmet Uckun, Evans We, C. J. Forsyth, KG Waddick, L Tuel-Ahlgren, Lisa M. Chelstrom, Anne L. Burkhardt, Joseph B. Bolen, Damian E. Myers · 发表于：Science · 年份：1995 · DOI：10.1126/science.7531365 · 被引用次数：277 · 研究领域：Acute Lymphoblastic Leukemia research、Chronic Lymphocytic Leukemia Research、T-cell and Retrovirus Studies

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.