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CAR-expressing T cells demonstrate impressive response rates hematological malignancies, but mediate limited anti-tumor efficacy in solid tumors. The T cell exhaustion-mediated dysfunction is an important barrier to progress, which raises the prospect that engineering exhaustion-resistant CAR-T cells could improve clinical outcomes.
Benefiting from advanced technology and years of experience, Creative Biolabs is gaining even greater success in developing innovative next-generation CAR-T products. We are proud to present a model CAR system - c-Jun overexpression-mediated T cell resistant to exhaustion, which is most likely to exert maximum anti-tumor efficacy in solid tumors, thereby addressing a major obstacle to this emerging therapeutic class.
c-Jun CAR Design
A theoretical basis for exhaustion in human T cells expressing CAR receptors is that because of an imbalance between activating and immunoregulatory AP-1-IRF complexes by inducing overexpression of c-Jun - an AP-1 family transcription factor associated with productive T cell activation. A paper published in the journal Nature in December 2019 confirmed this hypothesis.
To study the biology of exhaustion in T cells, the authors used a model system that induces fatigue by expressing the tone signal CAR. They designed a bicistronic CAR vector incorporating a JUN-P2A region, 14g2a-E101K scFv, which has shown enhanced amplification potential, enhanced functionality, reduced terminal differentiation and improvement antitumor efficacy in multiple in vivo models.
Fig.1 Schematic representation of c-Jun overexpressed CAR vector.
One-stop CAR Development Services
With state-of-art CAR development platforms and advanced technologies, Creative Biolabs is capable of offering CAR-T-cell development services. For the regular or custom CAR backbone construction, please refer to our related services: CAR Design & Construction. To further assess your c-Jun CAR biological efficacy (e.g., cytokine production, tumor killing, and CAR-T cell proliferation), our scientists can also provide comprehensive downstream services to complete your whole research. Please click CAR Cell In Vitro Assay Service, CAR-T Preclinical In Vivo Assay for more details.
Features of our Services
For more detailed information, please feel free to contact us or directly sent us an inquiry.
Reference
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