Polyspecific binding molecules and uses thereof

A method for preventing or treating a cancer in a mammal in which the cancer features pHLA-expressing tumor cells, the method comprising:

• a) administering to the mammal a single-chain polyspecific binding protein comprising at least one single-chain T-Cell receptor (sc-TCR) and at least one single-chain Fv (sc-Fv), wherein the sc-TCR specifically binds to a HLA complexed with a known peptide antigen on tumor cells and the sc-Fv specifically binds CD3 on the surface of immune cells, and wherein the sc-TCR comprises a V-β chain and a V-α chain covalently linked by a peptide linker and further comprises a C-β chain or fragment thereof fused to the C-terminus of the V-β chain;
• b) forming a specific binding complex through the single-chain polyspecific binding protein interactions with the known peptide antigen HLA complex on the tumor cells and with the CD3 molecule on the immune cells sufficient to activate the immune cells;
• and
• c) damaging or killing the tumor cells with the activated immune cells sufficient to prevent or treat the cancer in the mammal.