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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
Email: thierry.walzer@inserm.fr                                          
Centre International de Recherche en Infectiologie (CIRI), INSERM U1111                                           
and
Wenzheng JIANG
Email:wzjiang@bio.ecnu.edu
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University



SUMMERY


 
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 11, 2018
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