A CD123-specific chimeric antigen receptor augments anti-acute myeloid leukemia activity of Vγ9Vδ2 T cells

Author:

Zhang Xi1,Ang Wei Xia1,Du Zhicheng1ORCID,Ng Yu Yang1ORCID,Zha Shijun1,Chen Can1,Xiao Lin1,Ng Jia Yi2,Chng Wee Joo234,Wang Shu1

Affiliation:

1. Department of Biological Sciences, National University of Singapore, 117543, Singapore

2. Department of Haematology-Oncology, National University Cancer Institute Singapore, National University Health System, 119074, Singapore

3. Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore

4. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore

Abstract

Aim: To investigate whether anti-CD123 chimeric antigen receptor (CAR)-expressing Vγ9Vδ2 T cells could be an alternative for acute myeloid leukemia (AML) treatment. Materials & methods: Ex vivo expanded Vγ9Vδ2 T cells were electroporated with anti-CD123 CAR-encoding mRNA. The effector function and specificity of the modified Vγ9Vδ2 T cells were examined by in vitro cytotoxicity, degranulation and cytokine release level. The in vivo function was analyzed using the xenograft KG1-luc model with NOD-SCID-γc-/- mice. Results: The modified Vγ9Vδ2 T cells exhibited significantly improved effector activities against both AML cell lines and primary AML cells in vitro. In the xenograft mouse model, the modified Vγ9Vδ2 cells displayed an enhanced tumor control potency. Conclusion: Anti-CD123 CAR-expressing Vγ9Vδ2 T cells may serve as an alternative way to target AML.

Funder

Agency for Science, Technology and Research, Singapore

Singapore Ministry of Health's National Medical Research Council

Publisher

Future Medicine Ltd

Subject

Oncology,Immunology,Immunology and Allergy

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