@entity11603 ( @entity11603 ) is a good candidate molecule for the immunotherapy of B cell malignancies including @entity1072 ( @entity1072 ), because it may increase the capacity of the malignant cells to present @entity5 antigens. However, efforts to manipulate expression of the @entity1 @entity11603 ( @entity11603 ) molecule have foundered on problems associated with lack of consistent gene transfer into the malignant target cells. We now describe a new, highly reproducible method for inducing @entity11603 surface expression on malignant B cells, which is dependent on intercellular transfer of the @entity11603 protein from donor gene-modified fibroblasts to @entity1 @entity5 cells. Ten @entity1072 samples were cocultured with MRC-5 fibroblasts (a @entity1 embryonic lung cell line) previously transduced with an adenoviral vector encoding the @entity11603 gene. The malignant cells expressed high levels of surface @entity11603 , @entity12750 , and @entity2071 after coculture. Upregulation of @entity12750 was @entity1880 inhibitable and was a consequence of @entity2936 activation. However, inhibition of protein synthesis had no effect on the ability of @entity1072 cells to acquire surface expression of @entity11603 . @entity11603 surface expression required cell-to-cell contact, but was independent of @entity2936 engagement. @entity11603 transfer was not mediated by membrane fusion. The transferred @entity11603 was functionally intact and @entity1072 cells expressing this molecule induced increased @entity379 production from autologous peripheral blood T lymphocytes. This approach does not use any direct gene transfer to primary @entity1778 cells and can readily be scaled up for production of clinical @entity1072 vaccines.

Bystander transfer of functional @entity1 XXXX ligand from gene-modified fibroblasts to @entity1072 cells.

@entity1 :: ('9606', 'Species') :: ['human', 'patient'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity12750 :: ('941;942', 'Gene') :: ['B7-1 and B7-2', 'B7-1, B7-2'] @entity1880 :: ('MESH:D003513', 'Chemical') :: ['cycloheximide'] @entity2936 :: ('958', 'Gene') :: ['CD40'] @entity11603 :: ('959', 'Gene') :: ['CD40 ligand', 'CD40L', 'hCD40L'] @entity1072 :: ('MESH:D015451', 'Disease') :: ['B-chronic lymphocytic leukemia', 'B-CLL'] @entity1778 :: ('MESH:D007938', 'Disease') :: ['leukemia'] @entity379 :: ('3458', 'Gene') :: ['interferon-gamma'] @entity2071 :: ('3383', 'Gene') :: ['ICAM-1']
@entity2936 :: (958,Gene) :: ['CD40']
