NR4A Knock Out CAR-T Cell Development with CRISPR Technology

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As one of the current most popular immunotherapies, CAR-T therapy shows its strength by boosting the patients'own immune system to destroy cancer. Creative Biolabs has accumulated extensive experience in the discovery and development of optimized CAR-T therapies. Leverage the expertise of our experienced scientists to expedite and innovate your therapeutic CAR-T projects, we are inspired by NR4A target and are dedicated to providing NR4A knock out CAR-T cell development services.

Introduction of the Novel Target - NR4A

Recently, NR4A was identified as a key mediator of T cell dysfunction through genomic analysis, and also, NR4A transcription factors play the inhibitory role in CAR-T cell function in solid tumors. These two studies indicate that NR4A may be one of the potential targets to improve the CAR-T efficacy in solid tumors. Chen Dong's team used an in vitro T cell tolerance induction system to characterize genome-wide epigenetic and gene expression levels in tolerant T cell. Finally, they found that NR4A1 shows high expression levels in tolerant T cells. Moreover, NR4A1 deletion overcomes T cell tolerance and promote effector function, as well as enhancing anti-tumor and chronic virus immunity (see Fig.1 left). As a key regulator in the T cell dysfunction, NR4A1 is a potential target for tumor immunotherapy.

(left) Disruption of NR4A1 prevents T cell exhaustion caused by tumor and viral infection. (Liu, 2019); (right) NR4A-deficient CAR TILs promote tumor regression and prolong survival. (Chen, 2019)

Fig.1 (left) Disruption of NR4A1 prevents T cell exhaustion caused by tumor and viral infection. (Liu, 2019); (right) NR4A-deficient CAR TILs promote tumor regression and prolong survival. (Chen, 2019)

Joyce Chen's team found that NR4A triple knockout (NR4A1, NR4A2, NR4A3) CAR-T cells promoted tumor killing and improved the survival of tumor-bearing mice (see Fig.1 right). This indicates that NR4A inhibition can be as a promising strategy for cancer immunotherapy.

Our NR4A Knock Out CAR-T Cell Development Services

Over a decade of extensive experience in one-stop CAR-T cell therapy development, Creative Biolabs has established a series of solutions including Biomarker Identification & Selection, scFv Generation for CAR-T, CAR Design & Construction, CAR-T Gene Packaging & Delivery, In Vitro Assay Services, Preclinical In Vivo Assays, etc. Recently, our scientists developed cutting-edge CRISPR-Cas9 technology to edit CAR-T cells technology to edit CAR-T cells. Our CRISPR/Cas9 solution will help our clients to develop the highly efficient engineered CAR-T cells with improved anti-tumor efficacy. Based on our one-stop CAR-T cell development services and CRISPR/Cas9 technology, we are dedicated to providing NR4A knock out CAR-T cell development services to advance your CAR-T cell therapy to treat solid tumors.

NR4A Knock Out CAR-T Cell Development with CRISPR Technology

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As a leading CAR-T therapy development provider, Creative Biolabs is committed to guiding our clients in an end-to-end manner to ensure the optimal strategy and fit your expected features within budget and timeline. If you are interested in NR4A to knock out CAR-T cell development, please contact us for more information and a detailed quote.

References

Liu, Xindong, et al. "Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction." Nature (2019): 1.
Chen, Joyce, et al. "NR4A transcription factors limit CAR-T cell function in solid tumours." Nature (2019): 1.