This invention relates to mutant polypeptides comprising the IGF2 binding domain of the Insulin-like Growth Factor 2 Receptor (IGF2R) with residue P1597 is substituted for a different residue, for example H or K. Other residues which may be mutated include S1543, E1544, K1545, G1546, L1547, Q1569, S1602, G1603 and/or K1631. These IGF2 binding domains display dramatically increased binding affinity for IGF2 compared to both the wild-type and previously identified mutants and may be useful for example in cancer therapy.