SAv-drug conjugates yield CD45.2-ADCs that are cytotoxic against murine cell lines, primary HSCs, and primary AML cells. (A) Schema for production of SAv-drug conjugates and conjugation to biotinylated antibodies to produce ADCs. (B-D) Cytotoxicity assays of anti-CD45.2-ADC (biotinylated antibody plus SAv-drug conjugate), nb anti-CD45.2 plus free SAv-drug conjugate, or CD45.1-ADC (biotinylated isotype control plus SAv-drug conjugate) against (B) YAC-1 cells, (C) HSCs from B6 mice, and (D) AML1 primary leukemia cells (Dnmt3aR878H/+, FLT3-ITD+). Data points represent mean ± SEM of duplicate colony forming unit (CFU) plates (C) or triplicate wells (B,D) taken from 1 representative of at least 3 independent experiments. DBCO, dibenzocyclooctyne; IC50, 50% inhibitory concentration; SEM, standard error of the mean. nb, nonbiotinylated.