IL-15 (mouse)/IL-15Ra (Sushi) (mouse):Fc (silent) InVivoKine(TM)

Interleukin-15 (IL-15) is a cytokine that belongs to the interleukin-2 (IL-2) family and is essential for the development, proliferation and activation of immune cells, including natural killer (NK) cells, T cells and B cells. IL-15, unlike other cytokines, is widely expressed by many cell types including monocytes, macrophages, DC, fibroblasts, epithelial cells and skeletal muscle cells, but surprisingly not by T cells. IL-15 signals through a heterotrimeric receptor that is composed of the common gamma chain (gammac) subunit (CD132), the beta chain (betac) subunit (IL-2/IL-15R, CD122) and the IL-15 specific alpha subunit IL-15Ralpha (CD215). IL-15 binding to its trimeric receptor induces JAK1 activation which phosphorylates STAT3 via the beta chain, and JAK3 activation which phosphorylates STAT5 via the gamma chain. IL-15, like IL-2, stimulates the proliferation of T cells, induces the generation of cytotoxic lymphocytes and memory phenotype CD8 T cells, and stimulates the proliferation and maintenance of natural killer (NK) cells. In contrast to IL-2, IL-15 does not mediate activation-induced cell death (AICD) and does not consistently activate Tregs. If IL-2 is a promiscuously secreted molecule, IL-15 is locally secreted in small quantities where membrane-bound IL-15 induces signals at an immunological synapse. IL-15Ralpha (especially its sushi domain) acts more like a stabilizing and synergistic element (chaperone molecule) of IL-15, assisting IL-15 in its trans-presentation. The new recombinant protein IL-15 (mouse):IL-15Ra (Sushi) (mouse):Fc (LALA-PG)-KIH (human) (rec.) is an enhanced form of IL-15 with an extended half-life that stimulates the proliferation of T cells, B cells and NK cells in vivo, and increases its anti-tumor activity. The protein IL-15 (mouse):IL-15Ra (Sushi) (mouse):Fc (LALA-PG)-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-15 (mouse):Fc (LALA-PG) Knobs sequence (synthesizing a protein of 50kDa) and one encoding for the IL-15Ra (Sushi) (mouse):Fc (LALA-PG) Holes sequence (synthesizing a protein of 40kDa). Both vectors transfected into HEK 293 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-15 (mouse):IL-15Ra (Sushi) (mouse):Fc (LALA-PG)-KIH (human) (rec.). The LALA-PG mutations inhibit binding to FcgammaRs and C1q while FcRn binding and Fc stability remain unaffected. InVivoKinesTM are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.