IL-2 (human) (monomeric):Fc-KIH (human) (rec.)

Interleukin-2 (IL-2) is a 133 amino acid glycoprotein with one intramolecular disulfide bond and variable glycosylation. It is secreted by activated T cells and induces proliferation and maturation of activated T cells, natural killer cells and lymphokine activated killer cells. IL-2 also stimulates proliferation of antibody-producing B cells, activates neutrophils and induces mononuclear cells to secrete IFN-gamma and TNF-alpha and -beta. Moreover, studies have shown that IL-2 is required for activation-induced apoptosis, an important homeostatic mechanism in the immune system, which is involved in the maintenance of peripheral tolerance to self-antigens. IL-2 promotes T cell proliferation and particularly naive T cells. IL-2 signaling on activated T cells is effected through a quaternary high-affinity receptor complex consisting of IL-2, IL-2Ralpha (CD25), IL-2Rbeta and IL-2Rgamma. Naive T cells are relatively insensitive to IL-2 as they only express small amounts of IL-2Rbeta and IL-2Rgamma. They only acquire sensitivity after CD25 expression, which captures the cytokine and presents it to the IL-2Rbeta and IL-2Rgamma receptors. IL-2 is used in the treatment of metastatic cancer cells. Recently synergy has been observed between IL-2 based therapy and checkpoint blockade for cancer treatments. Cells which bear receptors for IL-2 stimulation are modulated by checkpoint inhibition either directly or through other lymphocytes, and lymphocytes which are effectors of checkpoint inhibition may respond to IL-2. The protein IL-2 (human) (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-2 (human):Fc Knobs sequence (synthesizing a protein of 45kDa) and one encoding for the Fc Holes sequence (synthesizing a protein of 28kDa). Both vectors transfected into HEK293 cells produce both Fc molecules (Knobs-into-Holes technology, J.B. Ridgway, et al., Protein Eng. 9, 617 (1996)) required for dimerization of the Fc moieties and for secretion of the final protein IL-2 (human) (monomeric):Fc-KIH (human) (rec.).