Antibodies have been engineered for enhanced cancer selectivity demonstrating preferential binding at low pH (139) or high ATP concentration (140). A company called BioAtla has recently leveraged 4- to 5-fold affinity improvement at low pH for EPCAM and CD3 binders (engineered through addition of histidine switches at the CDR/antigen interface) to generate a dual Conditionally Activated Bispecific (CAB) TCE against EPCAM (Figure 3) with a 10-fold in vitro killing window between pH 6.5 versus 7.4 (141). The gene discussed is EPCAM; the disease is cancer.