NKTR-255 + CD33.CAR natural killer cells

NKTR-255 + CD33.CAR natural killer cells is an investigational combination immunotherapy that pairs NKTR-255, a polymer-conjugated interleukin-15 (IL-15) receptor agonist designed to activate, expand, and prolong survival of natural killer (NK) cells and CD8+ T cells in vivo, with CD33-targeted chimeric antigen receptor (CAR)-engineered NK cells for the treatment of acute myeloid leukemia (AML). NKTR-255 enhances proliferation, persistence, and antitumor activity of adoptive cellular therapies by stimulating the IL-15 pathway, while CD33.CAR NK cells specifically recognize and kill CD33-expressing AML blasts using an anti-CD33 CAR construct incorporating costimulatory domains and IL-15 support sequences to improve NK cell function and persistence. Preclinical work presented in AML models has evaluated NKTR-255 as an immune-stimulatory cytokine add-on to CD33.CAR NK cell therapy to further augment antileukemic efficacy, building on clinical data showing that CD33.CAR NK cells alone can induce minimal residual disease–negative complete remissions in relapsed/refractory AML and that NKTR-255 can safely expand adoptively transferred CAR-modified lymphocytes.[1][2][5]