CATION-INDEPENDENT MANNOSE-6-PHOSPHATE RECEPTOR BINDERS FOR TARGETED PROTEIN DEGRADATION

The present invention relates to protein binding agents specifically binding the human cation-independent mannose-6-phosphate receptor (CI-M6PR), more specifically polypeptide agents comprising an immunoglobulin single variable domain (ISVD) specifically binding CI-M6PR at nano- to picomolar affinity, fused to further protein binding agents specifically binding extracellularly-accessible protein targets, such as membrane proteins, extracellular or secreted proteins. More specifically said CI-M6PR-specific ISVD recognizes CI-M6PR N-terminal domains 1, 2 and/or 3, thereby providing for means and methods for internalization, lysosomal targeting and degradation of agents comprising said ISVD, and of targets bound to said protein binding agents. The CI-M6PR binders disclosed herein are thus linked or fused to a further protein binding agent, in particular another antigen-binding protein, such as an ISVD or antibody, relevant for use in therapy, more specifically for treatment of diseases affected by said target antigen bound by said antigen-binding protein. More specifically disclosed herein are CI-M6PR ISVD fusions to antigen-binding proteins specifically binding EGFR, for treatment of cancer.