Tandem bispecific CD123/CLL‐1 CAR‐T cells exhibit specific cytolytic effector functions against human acute myeloid leukaemia

• DOI: 10.1111/ejh.14104
• Publication Date: 2023-09-15T12:33:19Z
• Authors: Xiang‐Yu Wang; Mei‐Ru Bian; Guo‐Qiang Lin; Lei Yu; Yan‐Ming Zhang; De‐Pei Wu
• Keywords: Interleukin-3 receptor; K562 cells

The treatment of refractory and recurrent acute myeloid leukaemia (AML) is still a challenge with poor response rates short survival times. In an attempt to solve this problem, we constructed tandem bispecific chimeric antigen receptor (CAR) targeting CD123 C-type lectin-like molecule 1 (CLL-1), two different AML antigens, verified its cytotoxic effects in vitro.We established cultured K562 cell lines expressing both CLL1 antigens. Single-target CAR-T cells specific were engineered, alongside CD123/CLL1 cells. Flow cytometry was used determine phenotypes, transfection efficiencies, cytokine release, CAR-T-cell proliferation, lactate dehydrogenase assay detect the cytotoxicity CD123/CLL-1 vitro.Two types exhibited significant killing on CLL-1 + CD123+ primary tumour efficiency case single expression comparable that target When faced dual cells, significantly surpass targeted killed CD123- CLL-1-positive released large number cytokines.CD123/CLL-1 can simultaneously demonstrating ability kill antigens multi-target This suggests exhibit advantages multiple wide range which may help overcome challenges posed by heterogeneity evasion mechanisms.