At Creative Biolabs, we are focused on the cutting-edge technologies, and our scientists are passionate about providing the novel and valuable solutions to promote the immunotherapy projects of our clients. To help our clients identify novel and potential immunotherapy targets, we established a powerful platform for the discovery of T cell activity modulators, especially T cell immune suppressor.
Immune evasion mechanisms in the TME of advanced human cancers are highly heterogeneous. Ample evidence supports that, in addition to the upregulation of B7-H1, many other molecular or cellular mechanisms can also contribute to dysfunctional immunity in TME. For some manipulation of the pathways which are not selective for TME, they could lead to a broad activation of the immune system with the risk of autoimmune toxicities. The current success of anti-PD therapy highlights the importance of restoring defective immune responses in the TME as a principle for normalization cancer immunotherapy. Based on the background, Lieping Chen’s team had identified Siglec-15 as a critical immune suppressor via a high-throughput screening for the discovery of T cell activity modulators. We are inspired by this technology and developed a powerful platform to help our clients identify novel T cell activity modulators as potential targets for normalization cancer immunotherapy.
A high-throughput functional screening system based on genome-scale T cell activity array (TCAA) was constructed to identify cell surface modulators of T cell activities in vitro (see Fig.1). This TCAA includes over 6000 human genes encoding more than 90% of human transmembrane proteins. The second key component of this platform is an artificial antigen-presenting cell line (aAPC) based on a 293T cell line. A membrane-associated anti-human CD3 (OKT3) single-chain variable fragment (scFv) was expressed in aAPC for T cell receptor stimulation. Also, several transmembrane signaling adapter genes such as DAP10, DAP12, CD3Z, etc. were expressed to facilitate membrane protein expression. The third measurement and monitoring component is Jurkat cell line expressed NF-κB/NFAT-GFP, or Jurkat-NFAT-Luc reporter cell line. The T cell activity enhancement or suppression effects will be measured by enhanced or decreased GFP expression, or luciferase activity. Through comparing to mock transfected controls, we will help you identify the T cell activity stimulator or suppressor for further normalization cancer immunotherapy discovery.
Fig.1 The principle of T cell activity array (TCAA) screening. (Wang, 2019)
This platform had been validated by our scientists via monitoring of some co-stimulatory or co-inhibitory molecules. We are dedicated to providing the most valuable solutions to our clients with consistent performance.
Our collaborative approach and deep scientific understanding of your project help us shape the best strategy for bringing the cutting-edge technology to facilitate your project. Our strong sense of purpose guide us to reach our clients’ goals with low risk and accelerated timelines. Creative Biolabs is committed to providing valuable solutions for our clients with high efficiency and great value. Please feel free to contact us to learn how we can be involved in your project.
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