CD33^KO-CD33-mesothelin Loop CAR design avoids fratricide and improves efficacy of iNK cells against acute myeloid leukemia.

ABSTRACT:

Background

Patients with acute myeloid leukemia (AML) are often older, which brings challenges of endurance and persistent efficacy of autologous chimeric antigen receptor (CAR)-T cell therapies. Allogenic CAR-natural killer (NK) cell therapies may offer reduced toxicities and enhanced anti-leukemic potential against AML. CD33 CAR-NK cells have been investigated for AML therapy. However, the fratricide-mediated lysis of CD33-expressing NK cells by CD33 CAR-NK cells limits the expansion and efficacy of CD33 CAR-NK cells. Mesothelin (MSLN), a tumor differentiation antigen, is highly expressed in a fraction of patients with AML, making it a promising target for AML therapy.

Methods

We designed a novel CD33-MSLN Loop CAR (Loop CAR) and evaluated its antitumor efficacy in human u

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12421167 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature