Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are critical for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. Nowadays, among the most promising approaches to activating therapeutic antitumor immunity is the blockade of immune checkpoints. Creative Biolabs has successfully launched an optimized Magic™ “humanized” animal platform to offer specialty humanized ICOS immune checkpoint knock-in mice for our clients all over the world.
ICOS Immune Checkpoint Pathway
ICOS (Inducible T-cell co-stimulator), also known as CD278, is a CD28-superfamily costimulatory molecule that is expressed on activated T cells as well as regulatory T cells. It is encoded by the ICOS gene. ICOS forms homodimers and plays a critical role in cell-cell signaling, immune responses, and regulation of cell proliferation, particularly for the survival and function of T cells, Th2 cell differentiation and for lung inflammatory responses. When interacts with its ligand ICOSL, ICOS can promote T cell production of several cytokines including IL-10, IL-4, IL-5, IFNg, and IL-17, depending on which cell type the effect dominates. Recently, it has been reported that the ICOS mediates interaction between tumor-infiltrating CD4C T cells and plasmacytoid dendritic cells (pDCs), which leads to the amplification of regulatory T cells (Tregs) and interleukin-10 secretion, then Tregs and pDCs that infiltrate primary breast tumors impair patient survival.
Fig.1. B7 Family of co-stimulatory and novel co-inhibitory molecules. (Ceeraz, et al., 2013)
What's more, it is reported that an agonistic stimulus for the ICOS pathway during anti-CTLA-4 therapy resulted in an increase in efficacy that was about four to five times as large as that of control treatments. CD28 is constitutively expressed on T cells, whereas ICOS and CTLA-4 expression are induced rapidly after T-cell activation. Previous studies demonstrated that expression of ICOS is regulated by both TCR and CD28 signals, while these signals are inhibited by a negative signal delivered by CTLA-4 engaged, and the expression of ICOS is positively correlated to that of CTLA4 and PD-1 on T cells.
Development of Humanized ICOS Immune Checkpoint Knock-In Mice
It is now well-defined that tumors select certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumor antigens. Since many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. With advanced technology and years of experience, Creative Biolabs has successfully established an array of well-characterized Magic™ “humanized” animal models, which can provide you with humanized immune checkpoint knock-in mouse models including humanized ICOS knock-in mouse. Our scientists are willing to assist you in your studies of anti-tumor immunotherapies. Please feel free to contact us for more detailed information.
Creative Biolabs also offers other various Humanized Mouse Models you may be interested in:
Reference
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