Rapid internalization of TMEFF2 in prostate cancer cells in culture. The TMEFF2 gene encodes a plasma membrane protein with limited normal tissue distribution and high overexpression in prostate cancer. The images show binding of a specific monoclonal antibody (mAb) to TMEFF2 protein on the surface of prostate cancer cells at 4^oC (upper panel), and the rapid and efficient internalization of the mAb-antigen complex at 37^oC (lower panel). Internalization is essential for an antibody-drug-conjugate (ADC) approach to cancer therapy, where drug release is dependent on lysosomal protease activity. A cathepsin B sensitive anti-TMEFF2 ADC was used to show specific cell killing and antitumor effects in prostate cancer xenograft models, validating it as a potential new therapy for the treatment of prostate cancer. For details, see 921 in this issue.