Traditional methods to eliminate cell populations by ADC or ADCC rely on the differential expression of unique targets to provide the specificity needed to reduce off-target toxicity. It is increasingly difficult to identify single cell surface targets to eliminate many cell types. The SNIPER™ approach utilizes unique target combinations that are selected to improve target specificity and eliminate new classes of cells by ADC, ADCC, or other mechanisms. During discovery, SNIPER™ fab arms are selected for diversity in epitope binding site and affinity. In-format high throughput discovery campaigns using cell binding assays are designed to identify candidates that can co-engage both targets to provide high avidity/specificity. Top candidates are optimized to maximize the difference between the monovalent binding affinity to each target and the bivalent avidity to the target combination.