Selective targeting of human lymphokine-activated killer cells by CD3
monoclonal antibody against the interferon-inducible high-affinity Fc gamma
RI receptor (CD64) on autologous acute myeloid leukemic blast cells
M Notter, WD Ludwig, S Bremer and E Thiel
Department of Hematology and Oncology, Free University of Berlin, Klinikum
Steglitz, Germany.
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 (19 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 1.5-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 OKT3-coated LAK cells is the high-affinity
Fc receptor for IgG (Fc gamma 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 IgG2a),
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 relapsed
AML cells by autologous T-cell clones correlated with the amount of target
cell expression of CD64; (4) anti-leukemic cytotoxicity of OKT3-coated T
cells could partially be inhibited by monomeric human Ig, the natural
ligand of CD64; and (5) expression of CD64 (Fc gamma RI) on fresh AML cells
could be increased by interferon-gamma (IFN-gamma) and IFN-alpha
translating into further enhancement of lysis by autologous OKT3-coated LAK
cells. Nonmalignant CD34+ cells sorted from peripheral blood were found to
lack expression of CD64 and hence were not affected by OKT3- triggered
T-cell targeting, as detected by colony formation assays. In conclusion,
the in vitro data presented provide a rationale for the combined clinical
use of recombinant interleukin-2, IFN-gamma, and low doses of CD3 MoAb to
eliminate AML cells while sparing nonmalignant hematopoietic progenitor
cells, for example, in the setting of purging procedures for autologous
bone marrow transplantation.
Volume 82,
Issue 10,
pp. 3113-3124,
11/15/1993
Copyright © 1993 by The American Society of Hematology
