Selective Targeting of Human Lymphokine-Activated Killer Cells by CD3 Monoclonal Antibody Against the Interferon-Inducible High-Affinity Fcy RI Receptor (CD64) on Autologous Acute Myeloid Leukemic Blast Cells

The potential of the CD3 monoclonal antibody (MoAb) OKT3 to selectively target lymphokine-activated killer (LAK) cells and T-cell clones in vitro against autologous tumor cells was studied using material from patients with acute leukemias (1 9 acute myeloid leukemias [AML], and 3 acute lymphoblastic leukemias [ALL]). Cytotoxicity mediated by patient LAK cells against AML blasts, but not against ALL cells and autologous Epstein-Barr virus-transformed B cells, was enhanced 1 .!&fold to 9.3-fold by OKT3 in all AML patients studied. The following findings suggest that the major target molecule on AML cells for OKT3coated LAK cells is the high-affinity Fc receptor for IgG (Fcy RI; CD64): (1) susceptibility to killing by OKT3-coated effector LAK cells segregated with target cell expression of CD64; (2) preincubation of AML blasts with monomeric OKT3 (murine lgG2a). the Fc portion of which is known to have preferential binding affinity to CD64, resulted in lysis by autologous T cells that were not spontaneously cytotoxic; (3) OKT3-dependent increase in lysis of primary and