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 with multiple myeloma activate allogeneic and autologous T cells. Results showed 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 class I, CD40, and a set of adhesion molecules. In accordance with the low density of B7 molecules on these cells, they were poor allogeneic CD8+ T cell stimulators. Neither IFN-gamma plus TNF-alpha nor CD40 stimulation significantly induced B7-1 or up-regulated B7-2 on human myeloma cell line or primary myeloma cells from six of seven patients. However, such induction was found on autologous bone-marrow nontumoral cells and on autologous dendritic cells following CD40 stimulation. High B7-1 expression was stably obtained on human myeloma cell line using transduction with a B7-1 retrovirus, enabling these cells to stimulate allogeneic CD8+, though not CD4+, T cell proliferation. For one patient with advanced disease, B7-1 gene transfer made it possible to amplify autologous cytotoxic T cells that killed autologous 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 promising immunotherapeutic approach in multiple myeloma.
Tarte
K
K
Institut National de la Santé et de la Recherche Médicale Unite 475, Montpellier, France.
Zhang
X G
XG
Legouffe
E
E
Hertog
C
C
Mehtali
M
M
Rossi
J F
JF
Klein
B
B
D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000951:Antigens, Neoplasm / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D007959:Lymphocyte Culture Test, Mixed; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D012190:Retroviridae / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D015815:Cell Adhesion Molecules; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens