Biparatopic polypeptides antagonizing Wnt signaling in tumor cells

A method of treatment of tumors expressing human LRP5 and/or human LRP6 by inhibition of the Wnt-1 and/or Wnt-3a signaling pathways in a cancer patient comprising administering to said patient a cross-reactive biparatopic polypeptide which specifically binds to an epitope of the human low-density receptor-like protein 5 (LRP5) as well as an epitope of the human low-density receptor-like protein 6 (LRP6) in an amount effective to reduce said patient's tumor burden and/or tumor size wherein said cross-reactive biparatopic polypeptide comprises:

• (a) a first immunoglobulin single variable domain, wherein said immunoglobulin single variable domain is a humanized VHH domain capable of inhibiting the Wnt1 signaling pathway comprising the CDR sequences:
• (SEQ ID NO:
• 4)
• CDR1:
• SYAMG
• (SEQ ID NO:
• 5)
• CDR2:
• AIRRSGRRTYYADSVKG
• and
• (SEQ ID NO:
• 6)
• CDR3:
• ARRVRSSTRYNTGTWWWEY;
• and
• (b) a second immunoglobulin single variable domain wherein said second immunoglobulin single variable domain is a humanized VHH domain capable of inhibiting the Wnt3a signaling pathway comprising the following CDR sequences:
• (SEQ ID NO:
• 13)
• CDR1:
• SYAMG
• (SEQ ID NO:
• 14)
• CDR2:
• AISWRSGSTYYADSVKG
• and
• (SEQ ID NO:
• 15)
• CDR3:
• DPRGYGVAYVSAYYEY.
• wherein said first and said second immunoglobulin single variable domains are covalently linked by a linker peptide, wherein said linker peptide comprises a third immunoglobulin single variable domain which binds to albumin comprising SEQ ID NO:24.