ERBB2 and neoplasm: Prolonged retention of HCT-mono-mIL12 on HER2-expressing cells due to a koff that is slower than the ke of HER2 on tumor cells can result in depletion via HER2-mediated endocytosis, followed by lysosomal degradation (Figure 6, step 3), as seen with antitumor Abs (38).