Costimulation of T-cell proliferation by a chimeric B7-antibody fusion protein.
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 B7-2(225)-scFv(FRP5) molecule, expressed in the yeast Pichia pastoris and purified from culture supernatants, binds to B7 counter-receptors and to ErbB2. B7-2(225)-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.
Gerstmayer
B
B
Institute for Experimental Cancer Research, Tumor Biology Center, Freiburg, Germany.
Hoffmann
M
M
Altenschmidt
U
U
Wels
W
W
D018033:Antibodies, Bispecific / Q000276:immunology*; D015793:HLA-B7 Antigen / Q000276:immunology*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D010843:Pichia / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D018033:Antibodies, Bispecific; D015793:HLA-B7 Antigen; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D011993:Recombinant Fusion Proteins