Polypeptides comprising immunoglobulin single variable domains targeting Glypican-3 and T cell receptor

A polypeptide that comprises an immunoglobulin single variable domain (ISVD) that specifically binds GPC3, wherein said ISVD comprises three complementarity determining regions (CDR1 to CDR3, respectively), and wherein the ISVD comprises:

• a) a CDR1 that comprises the amino acid sequence of SEQ ID NO:
• 7;
• a CDR2 that comprises the amino acid sequence of SEQ ID NO:
• 11 or an amino acid sequence with 1 amino acid difference with SEQ ID NO:
• 11, wherein the amino acid difference occurs at the fifth amino acid of SEQ ID NO:
• 11, and wherein any amino acid difference that occurs at the fifth amino acid of SEQ ID NO:
• 11 is selected from the group consisting of a substitution of lysine with glycine and a substitution of lysine with alanine;
• and a CDR3 that comprises the amino acid sequence of SEQ ID NO:
• 15,
• b) a CDR1 that comprises the amino acid sequence of SEQ ID NO:
• 8;
• a CDR2 that comprises the amino acid sequence of SEQ ID NO:
• 12 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO:
• 12, wherein the amino acid difference that occurs at the sixth amino acid of SEQ ID NO:
• 12 is a substitution of glutamate with aspartate, and wherein the amino acid difference that occurs at the ninth amino acid of SEQ ID NO:
• 12 is a substitution of tyrosine with asparagine;
• and a CDR3 that comprises the amino acid sequence of GVA,
• c) a CDR1 that comprises the amino acid sequence of SEQ ID NO:
• 32;
• a CDR2 that comprises the amino acid sequence of SEQ ID NO:
• 36 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO:
• 36, wherein the amino acid difference that occurs at the fifth amino acid of SEQ ID NO:
• 36 is selected from the group consisting of a substitution of lysine with glycine and a substitution of lysine with alanine, and wherein the amino acid difference that occurs at the eleventh amino acid of SEQ ID NO:
• 36 is a substitution of alanine with arginine;
• and a CDR3 that comprises the amino acid sequence of SEQ ID NO:
• 15, or
• d) a CDR1 that comprises the amino acid sequence of SEQ ID NO:
• 33;
• a CDR2 that comprises the amino acid sequence of SEQ ID NO:
• 37 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO:
• 37, wherein the amino acid difference that occurs at the sixth amino acid of SEQ ID NO:
• 37 is a substitution of glutamate with aspartate, and wherein the amino acid difference that occurs at the ninth amino acid of SEQ ID NO:
• 37 is a substitution of tyrosine with asparagine;
• and a CDR3 that comprises the amino acid sequence of GVA.