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Life Sciences (CAR-NK-92)

Characterization of the therapeutic role of T-BET or EOMES engineered CAR-NK-92 against B cell leukemia

The research project is under the co-supervision of

Thierry WALZER
Centre International de Recherche en Infectiologie (CIRI), INSERM U1111                                           
Wenzheng JIANG
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University


Lymphocytes engineered to express chimeric antigen receptor (CAR) are being celebrated as a major breakthrough in anticancer immunotherapy. CARs are usually expressed in T cells but there is a growing interest for CAR-NK cells. Clinical trials are under way to evaluate the therapeutic potential of modified CAR expressing NK cell lines such as the NK92 line.

Current limitations of CAR-T or CAR-NK strategies include the stability of the transferred cells and their trafficking to tumor sites. Our working hypothesis is that overexpression of the related T-box transcription factors T-bet and Eomes could overcome these limitations by inducing genes involved in NK cell proliferation and survival and by inducing receptors for pro-inflammatory chemokines expressed in the tumor bed.

Our project includes three tasks 1) the generation of modified NK92 lines over-expressing Tbet or Eomes or reciprocally knockout for these genes (T Walzer team Lyon); 2) the subsequent modification of these lines with the CAR , a second generation system targeting CD19 (W Jiang, Shanghai); 3) the treatment of mice previously inoculated with NALM6 lymphoma cells, with the modified CAR-NK92 cells and the comparison of the efficacy of the different cell lines generated in the project. The two laboratories are now connected through a PhD student (Jiang ZHANG), who is carrying out her PhD thesis as an exchange student between ENS-Lyon and ECNU.

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Last update October 31, 2018
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