Direct effect of bispecific anti-CD33 x anti-CD64 antibody on proliferation and signaling in myeloid cells

Bispecific anti-CD33 x anti-CD64 antibody (BsAb) directly inhibited proliferation and colony formation of human acute myeloid leukemia cell lines, without affecting the function of normal monocytes. Addition of BsAb to normal monocytes induced tyrosine phosphorylation. of Cb1 and Vav, association of these molecules with CD33, and downstream signaling. In leukemia cells that were insensitive to BsAb treatment, Vav and Cb1 were constitutively phosphorylated and, therefore, constitutively associated with CD33. Direct growth inhibition is an additional mechanism by which BsAb may be useful in the therapy of AML. (C) 2001 Elsevier Science Ltd. All rights reserved.