Recombinant Human ICOS-L-Fc Fusion Protein

Inducible Co-Stimulator Ligand (ICOS-L), also known as cluster of differentiation 275 (CD275) is a transmembrane protein that is mostly expressed by antigen-presenting cells. ICOS-L is classified as an immunostimulatory immune checkpoint. It binds ICOS (CD278) which is rapidly induced in CD4+ and CD8+ T cells upon their activation [1]. The interaction between ICOS and ICOS-L delivers a secondary co-stimulatory signal through the activation of the transcription factor AKT, which promotes T cell proliferation and differentiation as well as the production of cytokines [1]. In tumor immunity, ICOS is involved in the amplification of the anti-tumor cytotoxic CD8+ T cell response, as well as the 'pro-tumor' function and maintenance of regulatory T cells (Tregs). Therefore, both agonistic and antagonistic monoclonal antibodies (mAbs) targeting this pathway are being investigated in combinational cancer immunotherapy [2]. Notably, ICOS agonistic mAbs have been shown to potentiate the effects of anti-CTLA4 mAbs [3].

​References:

1. Amatore, F. et al. 2020. Role of ICOS in cancer immunotherapy. Expert Opin Biol Ther 20, 141-150.
2. Solinas, C. et al. 2020. The rationale behind targeting the ICOS-ICOS ligand costimulatory pathway in cancer immunotherapy. ESMO Open 5.
3. Soldevilla, M.M. et al. 2019. ICOS Costimulation at the Tumor Site in Combination with CTLA-4 Blockade Therapy Elicits Strong Tumor Immunity. Mol Ther 27, 1878-1891.