Selective targeting of human lymphokine-activated killer cells by CD3 monoclonal antibody against the interferon-inducible high-affinity Fcgamma RI receptor (CD64) on autologous acute myeloid leukemic blast cells

Item Type:	Article
Title:	Selective targeting of human lymphokine-activated killer cells by CD3 monoclonal antibody against the interferon-inducible high-affinity Fcgamma RI receptor (CD64) on autologous acute myeloid leukemic blast cells
Creators Name:	Notter, M. and Ludwig, W.D. and Bremer, S. and Thiel, E.
Abstract:	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.
Keywords:	CD34 Antigens, Cell Line, Immunologic Cytotoxicity, Hematopoietic Stem Cells, Interferon-gamma, Lymphokine-Activated Killer Cells, Acute Myeloid Leukemia , Muromonab-CD3, IgG Receptors
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	82
Number:	10
Page Range:	3113-3124
Date:	15 November 1993
Official Publication:	http://bloodjournal.hematologylibrary.org/cgi/content/abstract/82/10/3113
PubMed:	View item in PubMed

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