Single-chain variable fragment affinity tuning can optimize anti-AML CAR-NK cell functionality.

ABSTRACT:

Background

Natural Killer (NK) cells have intrinsic anticancer activity that can be redirected toward acute myeloid leukemia (AML) with chimeric antigen receptor (CAR) engineering. Here, we study the functional consequences of CAR binding affinity and targeted epitope on CAR-NK cell activation, cytolytic synapse formation, and antitumor activity.

Methods

We characterized NK-92 and primary NK cell populations expressing variant affinity AML-specific CARs containing single-chain variable fragments (scFvs, 26292 or 7G3) targeting two epitopes on CD123. 26292 affinity variants were discovered through directed evolution of an error-prone mutagenic library, while 7G3 affinity variants were previously reported. The resulting CAR-NK cell panel was studied with in vitro binding, acti

SUBMITTER: Rahnama R 

PROVIDER: S-EPMC11804205 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature