IL-2 (human) (Switch-2) (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. Activity of interleukin-2 (IL-2), is profoundly affected by pH, limiting IL-2 signaling within the acidic environment of tumors. A new designed IL-2, named Switch-2, binds the IL-2 receptor subunit IL-2Ralpha with higher affinity, triggers STAT5 activation and drives CD8+ T cell effector function more potently at acidic pH than at neutral pH. The protein IL-2 (human) (Switch-2) (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-2 (human) (Switch-2):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 and for secretion of the final protein IL-2 (human) (Switch-2) (monomeric):Fc-KIH (human) (rec.).