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Immunotherapy

TanCAR T cells targeting CD19 and CD133 efficiently eliminate MLL leukemic cells

Leukemia volume 32, pages 2012–2016 (2018)Cite this article

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Different strategies are underway to develop and optimize CARs to avoid relapses due to antigen loss [3]. One of these strategies is to use optimized CARs targeting multiple antigens in a Boolean OR-gate approach. Targeting multiple antigens allows these CARs to maintain their cytotoxic activity despite loss of one of the target cell antigens. One such approach is generation of a Tandem CAR (TanCAR), which uses two scFvs built in series in order to recognize two different targets [5]. This not only induces effective cytotoxicity when either of two antigens are presented but also synergistically enhances effector functions when both antigens are simultaneously encountered [5, 6]. This synergistic effect allows TanCAR to kill tumor cells expressing both antigens more efficiently than bystander cells expressing only one antigen. Therefore, we reasoned that TanCAR could be harnessed to not only eliminate CD19− MLL leukemic cells but also ameliorate CRS and decrease serum IL-6 levels by reducing “on-target, off-tumor” effects, ultimately preventing lineage switching. Based on this reasoning, we aimed to accomplish both goals by developing a novel TanCAR to address CD19 antigen loss in MLL-rearranged B-ALL.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2018YFA0107802), the National Natural Science Foundation of China (81570119 and 81370651), the Shu Guang project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (14SG15), the Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant (20161304), the Innovation Fund Projects of Shanghai Jiao Tong University (BXJ201809), and the Samuel Waxman Cancer Research Foundation.

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  1. These authors contributed equally: Dan Li, Yutian Hu, Zhen Jin, You Zhai

Affiliations

  1. State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, School of Medicine and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Collaborative Innovation Center of Systems Biomedicine, Collaborative Innovation Center of Hematology, Shanghai 200025, China

    Dan Li, Yutian Hu, Zhen Jin, You Zhai, Yuting Tan, Yan Sun, Shouhai Zhu, Chunjun Zhao, Bing Chen, Jiang Zhu, Zhu Chen, Saijuan Chen, Junmin Li & Han Liu

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  1. Dan Li
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  2. Yutian Hu
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  14. Han Liu
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Correspondence to Han Liu.

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Li, D., Hu, Y., Jin, Z. et al. TanCAR T cells targeting CD19 and CD133 efficiently eliminate MLL leukemic cells. Leukemia 32, 2012–2016 (2018). https://doi.org/10.1038/s41375-018-0212-z

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