Margaret C Lunn-Halbert, George S Laszlo, Sarah Erraiss, Mark T Orr, Heidi K Jessup, Heather J Thomas, Henry Chan, Mahan A Jahromi, Jonathan Lloyd, Ann F Cheung, Gregory P Chang, Tanmay Dichwalkar, Daniel Fallon, Asya Grinberg, Eduardo Rodríguez-Arbolí, Sheryl Y T Lim, Allie R Kehret, Jenny Huo, Frances M Cole, Samuel C Scharffenberger, Roland B Walter
Increasing efforts are focusing on natural killer (NK) cell immunotherapies for AML. Here, we characterized CC-96191, a novel CD33/CD16a/NKG2D immune-modulating TriNKET® . CC-96191 simultaneously binds CD33, NKG2D, and CD16a, with NKG2D and CD16a co-engagement increasing the avidity for, and activation of, NK cells. CC-96191 was broadly active against human leukemia cells in a strictly CD33-dependent manner, with maximal efficacy requiring the co-engagement of CD16a and NKG2D. A frequent CD33 single nucleotide polymorphism, R69G, reduced CC-96191 potency but not maximal activity, likely because of reduced CD33 binding...
February 22, 2024: Cancers