Targeting of a B7-1 (CD80) immunoglobulin G fusion protein to acute myeloid leukemia blasts increases their costimulatory activity for autologous remission T cells

Transfection of tumor cells with the gene encoding the costimulatory molecu le 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 immun ity. As an alternative approach, this study analyzed the costimulatory capa city 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 blast s (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 pro tein used in this study efficiently costimulated the proliferation of resti ng and preactivated T cells when immobilized on plastic. After preincubatio n with B7-1 IgG, specific binding of the fusion protein to the high-affinit y Fc<gamma>receptor I (CD64) on leukemic cells was demonstrated and was fou nd to increase the proliferation of both allogeneic and autologous T cells in costimulation experiments. Furthermore, targeting of B7-1 IgG to the tum or membrane resulted in increased proliferation of autologous remission T c ells and had the potential to generate an enhanced redirected cytotoxic T-c ell response against autologous AML blasts. In summary, the targeting of B7 -1 IgG fusion protein described in this study represents a strategy alterna tive to gene therapy to restore the expression of the costimulatory molecul e B7-1 on human AML blasts, thereby enhancing their immunogenicity for auto logous T cells. This new approach may have implications for T-cell-mediated immunotherapy in AML. (Blood. 2001;97: 3138-3145) (C) 2001 by The American Society of Hematology.