REDIRECTING THE COMPLETE T CELL RECEPTOR/CD3 SIGNALING MACHINERY TOWARDS NATIVE ANTIGEN VIA MODIFIED T CELL RECEPTOR

We show that a chimeric T cell receptor (TCR) β chain consisting of a single-chain Fv portion derived from a monoclonal antibody and the full TCR β chain is able to assemble functionally with endogenous TCR/CD3 components and transfer the antibody specificity as well as the TCR specificity into TCRβ− as well as into TCRβ+ T cells. This allows the incorporation new non-major histocompatibility complex-restricted ligand specificities into the intact TCR/CD3 complex which can exploit the full range of biological activities of the endogenous TCR signaling machinery. This approach can provide wider opportunities to redirect T cells to virus or tumor antigen-bearing cells.