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. (April 2016)

• Record Type: Journal Article
• Authors: Gao, Catherine; Leyton, Jeffrey V.; Schimmer, Aaron D.; Minden, Mark; Reilly, Raymond M.
• Is Part Of: Applied radiation and isotopes. Volume 110(2016:Apr.)
• Page Start: 1
• Page End: 7
• Publication Date: 2016-04
• Subjects: Acute myeloid leukemia (AML) -- Radioimmunotherapy -- Indium-111 -- CD123 -- Auger electrons -- Nuclear translocation sequences (NLS); Radiology -- Periodicals; Radiation -- Industrial applications -- Periodicals; Nuclear chemistry -- Periodicals; Internet resource; Periodical; 660.298
• DOI: 10.1016/j.apradiso.2015.12.043
• Languages: English
• ISSNs: 0969-8043

Abstract

Abstract: Chimeric IgG1 monoclonal antibody CSL360 recognizes the CD123 + /CD131 − phenotype expressed by leukemic stem cells (LSC). Auger electron-emitting 111 In-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. 111 In-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 111 In-DTPA-NLS-CSL360 up to 3.7-fold. Isotype control 111 In-DTPA-chIgG1 was 2-fold less cytotoxic, and unlabeled CSL360, DTPA-NLS-CSL360 or free 111 In acetate did not decrease cell survival. These results are promising for further evaluation of 111 In-DTPA-NLS-CSL360 for Auger electron radioimmunotherapy of AML targeting the critical LSC subpopulation. Highlights: 111 In-DTPA-NLS-CSL360 the CD123 + /CD131 − phenotype of leukemic stem cells (LSC). 111 In-DTPA-NLS-CSL360 was bound, internalized and imported into the nucleus of AML-5 leukemia cells. 111 In-DTPA-NLS-CSL360 reduced the clonogenic survival of AML-5 leukemia cells by 4-fold.