Multifunctional natural killer (NK) cell engagers binding to NKp46 and CD123

A binding protein comprising a first and a second antigen binding domain (ABD) and all or part of an immunoglobulin Fc region or variant thereof, wherein each of said ABD comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein each VH and VL comprises three complementary determining regions (CDR-1 to CDR-3);

• and wherein:
• (i) the first ABD binds specifically to human CD123 and comprises:
• a VH1 comprising a CDR-H1, H2 and H3 comprising the amino acid sequences of SEQ ID NO:
• 1 to 3 respectively or comprising the amino acid sequences of SEQ ID NO:
• 4 to 6 respectively, and
• a VL1 comprising a CDR-L1, L2 and L3 comprising the amino acid sequences of SEQ ID NO:
• 7 to 9 respectively or comprising the amino acid sequences of SEQ ID NO:
• 10 to 12 respectively;
• (ii) the second ABD binds specifically to human NKp46 and comprises:
• a VH2 comprising a CDR-H1, 2 and 3 comprising:
• the amino acid sequences of SEQ ID NO:
• 13 to 15 respectively;
• the amino acid sequences of SEQ ID NO:
• 16 to 18 respectively;
• the amino acid sequences of SEQ ID NO:
• 19 to 21 respectively;
• the amino acid sequences of SEQ ID NO:
• 22 to 24 respectively;
• or
• the amino acid sequences of SEQ ID NO:
• 16, 25 and 26 respectively;
• and
• a VL2 comprising a CDR-L1, 2 and 3 comprising:
• the amino acid sequences of SEQ ID NO:
• 27 to 29 respectively;
• the amino acid sequences of SEQ ID NO:
• 30 to 32 respectively;
• the amino acid sequences of SEQ ID NO:
• 33 to 35 respectively;
• the amino acid sequences of SEQ ID NO:
• 36 to 38 respectively;
• or
• the amino acid sequences SEQ ID NO:
• 39, 31 and 40 respectively;
• and wherein all or part of the immunoglobulin Fc region or variant thereof binds to a human Fc-γ receptor.