Abstract: Acute myeloid leukemia (AML) is characterized by defective blood cell maturation and accumulation of myeloblasts in marrow and blood. Despite numerous efforts in developing treatments for AML over the past decades, the prognosis remains unsatisfactory with relapse observed in about 50% of the patients. CD123 is a well-studied therapeutic target for AML, with several ongoing clinical trials involving Car-T cells, T cell recruiter, antibody-drug conjugate, etc. However, CD123 antibodies displayed limited efficacy, while T cell-related therapies tend to induce severe toxicity. In this article, researchers developed a trifunctional natural killer cell engager that targets CD123 on AML blasts and two activating receptors on the natural killer cell (CD123-NKCE). This trifunctional antibody is tested in vitro and in murine, offering better antitumor activity than a CD123-antibody while showing less cytokine release than a T cell engager. A pharmacokinetics study was performed in cynomolgus monkeys with no adverse effects observed, supporting the potential for clinical development of CD123-NKCE.
Reference: Gauthier, L., Virone-Oddos, A., Beninga, J. et al. Control of acute myeloid leukemia by a trifunctional NKp46-CD16a-NK cell engager targeting CD123. Nat Biotechnol (2023). https://doi.org/10.1038/s41587-022-01626-2
Originally published at chemistry.nd.edu.