The present disclosure relates to anti-HER2 constructs, such as Fc polypeptide dimer-antibody variable region fusion proteins, that cross the BBB and bind to HER2 in the brain parenchyma. In some embodiments, the anti-HER2 constructs (e.g., Fc polypeptide dimer-antibody variable region fusion proteins) retain effector function upon binding to HER2, but do not substantially deplete reticulocytes in vivo. The present disclosure also relates to methods for transcytosing an anti-HER2 antibody variable region across the BBB and treating HER2-positive cancers and metastatic lesions thereof.
ANTI-HER2 POLYPEPTIDES AND METHODS OF USE THEREOF