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Blood, 15 May 2001, Vol. 97, No. 10, pp. 3138-3145
IMMUNOBIOLOGY
Targeting of a B7-1 (CD80) immunoglobulin G fusion protein to
acute myeloid leukemia blasts increases their costimulatory activity
for autologous remission T cells
Michael Notter,
Tim Willinger,
Ulrike Erben, and
Eckhard Thiel
From the Department of Hematology and Oncology, Freie
Universität Berlin, Universitätsklinikum Benjamin Franklin,
Berlin, Germany.
Transfection of tumor cells with the gene encoding the
costimulatory molecule B7-1 (CD80), the ligand for CD28 and cytotoxic T
lymphocye antigen-4 on T cells, has been shown to result in potent
T-cell-mediated antitumor immunity. As an alternative approach, this
study analyzed the costimulatory capacity of a human B7-1 immunoglobulin G (IgG) fusion protein targeted to the cell
membrane of human acute myeloid leukemia (AML) blasts. Flow cytometric analysis revealed a low constitutive expression of B7-1 on human AML
blasts (on average, 3.0 ± 4.3%; n = 50). In contrast, the expression of B7-2 (CD86) was highly heterogeneous and higher in AML
blasts of French-American-British classification types M4 and M5
(P < .0001). The B7-1 IgG fusion protein used in this study efficiently costimulated the proliferation of resting and preactivated T cells when immobilized on plastic. After preincubation with B7-1 IgG, specific binding of the fusion protein to the
high-affinity Fc receptor I (CD64) on leukemic cells was
demonstrated and was found to increase the proliferation of both
allogeneic and autologous T cells in costimulation experiments.
Furthermore, targeting of B7-1 IgG to the tumor membrane resulted in
increased proliferation of autologous remission T cells and had the
potential to generate an enhanced redirected cytotoxic T-cell response
against autologous AML blasts. In summary, the targeting of B7-1 IgG
fusion protein described in this study represents a strategy
alternative to gene therapy to restore the expression of the
costimulatory molecule B7-1 on human AML blasts, thereby enhancing
their immunogenicity for autologous T cells. This new approach may have
implications for T-cell-mediated immunotherapy in AML.
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