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

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Title: Characterization of the therapeutic role of T-BET or EOMES engineered CAR-NK-92 against B cell leukemia
Directors: Thierry WALZER & Wenzheng JIANG 
Discipline: Life science
Status: Incubating Project
Starting date: 2018

Supervision

Summary

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. 

Subject(s)