Auger electron-emitting 111In-DTPA-NLS-CSL360 radioimmunoconjugates are cytotoxic to human acute myeloid leukemia (AML) cells displaying the CD123+/CD131− phenotype of leukemia stem cells

Chimeric IgG1 monoclonal antibody CSL360 recognizes the CD123+/CD131− phenotype expressed by leukemic stem cells (LSC). Auger electron-emitting 111In-DTPA-NLS-CSL360 radioimmunoconjugates incorporating nuclear translocation sequence (NLS) peptides bound specifically to Raji cells transfected with CD123 and exhibited a KD of 11 nmols/L in a competition receptor-binding assay using CD123-transfected CHO cells. 111In-DTPA-NLS-CSL360 was bound, internalized and transported to the nucleus of human AML-5 myeloid leukemia cells. The clonogenic survival of AML-5 cells was reduced by 111In-DTPA-NLS-CSL360 up to 3.7-fold. Isotype control 111In-DTPA-chIgG1 was 2-fold less cytotoxic, and unlabeled CSL360, DTPA-NLS-CSL360 or free 111In acetate did not decrease cell survival. These results are promising for further evaluation of 111In-DTPA-NLS-CSL360 for Auger electron radioimmunotherapy of AML targeting the critical LSC subpopulation.