COSTIMULATION OF T-CELL PROLIFERATION BY A CHIMERIC B7-ANTIBODY FUSION PROTEIN

T cells require at least two signals for activation and clonal expansi on. The first signal conferring specificity is initiated by interactio n of the T cell receptor with peptide-bearing MHC molecules. The secon d, costimulatory signal can be provided by cell-surface molecules on a ntigen-presenting cells such as B7-1 (CD80) and B7-2 (CD86), which int eract with CD28 on T cells. To direct the costimulatory B7-2 molecule to the surface of tumor cells we have constructed a chimeric fusion pr otein, which consists of the extracellular domain of human B7-2 fused to a single-chain antibody domain (scFv) specific for the ErbB2 protei n, a type I growth factor receptor overexpressed in a high percentage of human adenocarcinomas. This B7-2(225)-scFv(FRP5) molecule, expresse d in the yeast Pichia pastoris and purified from culture supernatants, binds to B7 counter-receptors and to ErbB2. B7-2(225)scFv(FRP5) local izes specifically to the surface of ErbB2-expressing target cells, the reby providing a costimulatory signal, which results in enhanced proli feration of syngeneic T cells.