Both ICAM1 ADCs have bystander killing effects by utilizing protease-cleavable linkers of dipeptide (Val–Cit) or quadrapeptide (Gly-Gly-Phe-Gly), which can rapidly release ADC warheads from ICAM1+ CCA cells to surrounding ICAM1- tumor cells and stromal cells including tumor-associated macrophages or fibroblasts. The gene discussed is ICAM1; the disease is cholangiocarcinoma.