Costimulation of T-cell proliferation by a chimeric B7-antibody fusion protein
B Gerstmayer, M Hoffmann, U Altenschmidt… - Cancer Immunology …, 1997 - Springer
B Gerstmayer, M Hoffmann, U Altenschmidt, W Wels
Cancer Immunology, Immunotherapy, 1997•SpringerT cells require at least two signals for activation and clonal expansion. The first signal
conferring specificity is initiated by interaction of the T cell receptor with peptide-bearing
MHC molecules. The second, costimulatory signal can be provided by cell-surface
molecules on antigen-presenting cells such as B7-1 (CD80) and B7-2 (CD86), which
interact with CD28 on T cells. To direct the costimulatory B7-2 molecule to the surface of
tumor cells we have constructed a chimeric fusion protein, which consists of the extracellular …
conferring specificity is initiated by interaction of the T cell receptor with peptide-bearing
MHC molecules. The second, costimulatory signal can be provided by cell-surface
molecules on antigen-presenting cells such as B7-1 (CD80) and B7-2 (CD86), which
interact with CD28 on T cells. To direct the costimulatory B7-2 molecule to the surface of
tumor cells we have constructed a chimeric fusion protein, which consists of the extracellular …
Abstract
T cells require at least two signals for activation and clonal expansion. The first signal conferring specificity is initiated by interaction of the T cell receptor with peptide-bearing MHC molecules. The second, costimulatory signal can be provided by cell-surface molecules on antigen-presenting cells such as B7-1 (CD80) and B7-2 (CD86), which interact with CD28 on T cells. To direct the costimulatory B7-2 molecule to the surface of tumor cells we have constructed a chimeric fusion protein, which consists of the extracellular domain of human B7-2 fused to a single-chain antibody domain (scFv) specific for the ErbB2 protein, a type I growth factor receptor overexpressed in a high percentage of human adenocarcinomas. This B7-2225-scFv(FRP5) molecule, expressed in the yeast Pichia pastoris and purified from culture supernatants, binds to B7 counter-receptors and to ErbB2. B7-2225-scFv(FRP5) localizes specifically to the surface of ErbB2-expressing target cells, thereby providing a costimulatory signal, which results in enhanced proliferation of syngeneic T cells.
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