Goat anti Equine IL2 polyclonal antibody [Biotin]

The transcription factor nuclear factor of activated T cells (NFAT) has a key role in both T cell activation and tolerance and has emerged as an important target of immune modulation. NFAT directs the effector arm of the immune response in the presence of activator protein-1 (AP-1), and T cell anergy/exhaustion in the absence of AP-1. Envisioning a strategy for selective modulation of the immune response, we designed a FRET-based high-throughput screen to identify compounds that disrupt the NFAT: AP-1: DNA complex. We screened similar to 202,000 small organic compounds and identified 337 candidate inhibitors. We focus here on one compound, N-(3-acetamidophenyl)-2-[5-(1H-benzimidazol-2-yl)pyridin-2-yl] sulfanylacetamide (Compound 10), which disrupts the NFAT: AP-1 interaction at the composite antigen-receptor response element-2 site without affecting the binding of NFAT or AP-1 alone to DNA. Compound 10 binds to DNA in a sequence-selective manner and inhibits the transcription of the Il2 gene and several other cyclosporin A-sensitive cytokine genes important for the effector immune response. This study provides proof-of-concept that small molecules can inhibit the assembly of specific DNA-protein complexes, and opens a potential new approach to treat human diseases where known transcription factors are deregulated.

T cells have been successfully applied to cancer immunotherapy. However, a challenge is an expansion of T cells from cynomolgus monkey, which is a valuable non-human primate model for T cell therapy transferring to the clinic. Here, we compared several strategies to expand cynomolgus monkey T cell and developed an appropriate method. Our study demonstrated that 100 ng/ml CD3 mAb + 1% PHA+ 1000 U/ml IL2 therapy significantly expanded peripheral blood CD3+ T cells without compromising T cell phenotype in vitro. The results of this study could be used for T cell remodeling, which has significant therapeutic potential in Chimeric Antigen Receptor-T (CAR-T) cell immunotherapy.