Development of a high affinity Anticalin<sup>®</sup> directed against human CD98hc for theranostic applications
Friedrich‐Christian Deuschle, Volker Morath, A. Schiefner, Corinna Brandt, Simone Ballke, Sybille Reder, Katja Steiger, Markus Schwaiger, Wolfgang Weber, Arne Skerra
Abstract
Enhanced amino acid supply and dysregulated integrin signaling constitute two hallmarks of cancer and are pivotal for metastatic transformation of cells. In line with its function at the crossroads of both processes, overexpression of CD98hc is clinically observed in various cancer malignancies, thus rendering it a promising tumor target. Methods: We describe the development of Anticalin proteins based on the lipocalin 2 (Lcn2) scaffold against the human CD98hc ectodomain (hCD98hcED) using directed evolution and protein design. X-ray structural analysis was performed to identify the epitope recognized by the lead Anticalin candidate. The Anticalin -with a tuned plasma half-life using PASylation technology -was labeled with 89 Zr and investigated by positron emission tomography (PET) of CD98-positive tumor xenograft mice.