Matchmaking gene therapy with mimetic antibodies

T cells expressed a diversity of T-cell receptors, verifying polyclonality.Notably, increasing proportions of activated NK cells 9 were observed following CD371/SAVVY/IL-18 CAR T-cell therapy, again predominantly in responding patients.It will be interesting to determine whether the emergence of this population is secondary to NK-cell binding of activating ligands on the AML blasts 10 or because of direct stimulation of NK cells by CAR T-cell-derived IL-18.Regardless of the exact mechanism, the increase in cytotoxic NK cells in patients treated with CD371/SAVVY/IL-18 CAR Tcell therapy is likely a unique secondary effect that amplifies the anti-AML activity of this product.Overall, treatment of patients with AML refractory to standard therapy using CD371/SAVVY/IL-18 CAR T cells is a novel approach.Modulation of the AML-associated immune microenvironment, including activation of cytotoxic NK cells, is an important advance in this challenging disease.Although the observed response rate is certainly thrilling, these responses were not sustained and incomplete disease clearance together with a lack of functional CAR T-cell persistence were likely contributory to disease relapse.Even so, the data from this small cohort of patients are supportive of further testing and development of CD371/SAVVY/IL-18 CAR T-cell therapy guided by paired biological study as treatment for patients who otherwise have extremely limited therapeutic options.Conflict-of-interest disclosure: C.L.B. has been awarded and has pending patent applications describing the use of engineered T and NK cells as therapeutics.M.T.