Induced expression of B7-1 on myeloma cells following retroviral gene transfer results in tumor-specific recognition by cytotoxic T cells

The aim of this study was to evaluate whether tumor cells from patients wit h multiple myeloma activate allogeneic and autologous T cells. Results show ed that myeloma cells expressed few B7-2 and no B7-1 in six cell lines and primary cells from 11 patients. They expressed substantial levels of HLA cl ass I, CD40, and a set of adhesion molecules. In accordance with the low de nsity of B7 molecules on these cells, they were poor allogeneic CD8(+) T ce ll stimulators. Neither IFN-gamma plus TNF-alpha nor CD40 stimulation signi ficantly induced B7-1 or up-regulated B7-2 on human myeloma cell line or pr imary myeloma cells from six of seven patients. However, such induction was found on autologous bone-marrow nontumoral cells and on autologous dendrit ic cells following CD40 stimulation, High B7-1 expression was stably obtain ed on human myeloma cell line using transduction with a B7-1 retrovirus, en abling these cells to stimulate allogeneic CD8(+), though not CD4(+), T cel l proliferation. For one patient with advanced disease, B7-1 gene transfer made it possible to amplify autologous cytotoxic T cells that killed autolo gous myeloma cells in an HLA class I-restricted manner, but not autologous PHA blasts, These results suggest that B7-1 gene transfer could be a promis ing immunotherapeutic approach in multiple myeloma.