IL27 cell screening model
IL-27 was discovered in 2002, consisting of two non-covalent-priced subunits: IL-27P28 (P28) and EB virus-induced molecular 3 (EBI3). The subunit and IL-6 have homology. According to the results of the sequence comparison, the P28 subunit of the IL-27 and the P35 sub-in IL-12 have about 64%of amino acid homologous; and the P28 also has about 27%of the homology with IL-6; in addition, EBI3 It has about 33%of amino acid homology as IL-12P40. IL-27 is combined with heterogeneous dicent receptors consisting of GP130 and IL27ra (WSX-1). IL27RA (WSX-1) is highly expressed on lymphocytes, and there is low expression on osteomycosis; GP130 is widely spewed on cells, so the specificity of IL-27 activity is of IL27ra (WSX-1) and GP130 The common expression decision, although in the absence of GP130, IL-27 can combine IL27ra (WSX-1) with low relatives. In addition, IL27RA (WSX-1) and GP130 can also exist in soluble forms (SWSX-1 and SGP130), and the combination of SWSX-1 and IL-27 plays the role of signal antagonists. It is interesting Yes, the SGP130 does not suppress the IL-27 signal transmission, although it can block IL-11 and IL-6 transmission, which suggests that the SGP130 may only inhibit the GP130 homologous dirais signal transmission. When IL-27 is binding with its receptor, the STAT family transcription factors in the lower stat family will phosphate and activate the STATS pathway. This activation may be affected by the cell type.
IL-27 is generated by the TOLL-like body (TLR) activation. , Especially in suppressing TH2, TH17 and Treg differentiation; however, some recent studies have shown that IL-27 can promote the growth and survival of TREG cells. Because the IL-27 generated by TLR activates also regulates the function of myel cells and leads to the upsurge of TLR expression on these cells, which indicates that the IL-27 may participate in a positive feedback circuit. The bone marrow cells and epithelial cells processed by IL-27 are also enhanced by raising MHC I and II and co-stimulating molecules to show the ability of antigen presentation. Due to its ability to influence the antigen and regulate the auxiliary T cell differentiation and activation, IL-27 may be an important regulatory factor in the micro-environment of the tumor.
IL-27 and disease
Existing studies have shown that IL-27 is a dual-functional cytokines. In different physiological and pathological conditions, it may be used as an immune activation factor to promote immune activation and inflammation. It can also be used as a kind of type. As an immunosuppressive factors, inhibit immune response and resist inflammation. Therefore, the IL-27 may affect the development of various diseases such as cancer, infectious diseases, and autoimmune diseases through different biological functions. In addition, the latest research also found that IL-27 can directly act on fat cells, promote its heat production and energy consumption, and indicates that it is also correlated with metabolic diseases such as obesity and metabolic diseases such as type 2. Therefore, IL-27 may become multiple types Potential targets of diseased drug development.
IL-27 antibody drug and tumor immunity
Existing studies have shown that IL-27, as a kind of immune examination point factor, can regulate the immunosuppressing and exhaustion of T cells in tumor microenvironment. For example, IL-27 can induce monocytes and tumor-related macrophages, as well as the expression of human prostate, breast and lung cancer cells. The IL-27 signal in cancer cells also activate STAT1/STAT3 and induce the component expression of IDO. These expression changes will enhance the immune escape ability of tumor cells. Similar research on the lymph tumor cell system also shows that the enhancement of IL-27 in tumor cells will increase the expression of PD-L1 on tumor-related macrophages; and IL-27 signals on tumor cells will induce PD- The expression of L1, the generation of IL-10, TGF-β, and the expression of MHCI are lowered; ) In the expression, these factors will enhance the depletion of the effect T cell, and blocking the IL-27 signal will cause NFIL3 and TIM-3 to reduce expression and reduce T cells. It is conducive to the amplification of TREG cells, and the Treg cells after IL-27R knockout cannot inhibit antitumor immunity in the melanoma mice model; the IL-27 secreted by the neutral particles infiltrated by tumor will increase the expression of CD39 on the IL-27. And enhance the immunosuppressive ability of CD163+macrophages. These studies have shown that IL-27 and its signal pathway may be an important potential target for tumor immunotherapy.
The IL-27 monoclonal anti-anti-anti-drug SRF388 developed by Surface Oncology is currently the only IL-27 targeted drug that has entered clinical development in the world. It is also the first IL-27 monoclonal antibody to enter the phase II clinical verification stage. It can pass through Block the interaction of IL-27 and its receptor IL-27ra, inhibit all downstream signals in the Jak-STAT pathway, and promote immune activation in the micro-environment of tumor. At present, the drug has carried out multiple clinical experiments for non-small cell lung cancer, single drugs for liver cancer, and anti-VEGF antibodies, anti-VEGF antibodies, and initially observed a certain clinical effect.
IL-27 cell screening model
For the development of IL-27 and related signaling pathways, we have also developed the reporting gene cell screening model of IL-27 in a timely manner, which can be used to evaluate the drug activity of cell levels and help the research and development of related drugs.
IL27 Effector Reporter Cell RQP74199
Figure 1.Dose Response of Recombinant Human lL27 in IL27 Effector Reporter Cells (C18).
