IL-2 (human) Superkine H9T (monomeric):Fc-KIH (human) (rec.)

IL-2 Superkine H9T (monomeric):Fc Knobs-into-Holes (human) (rec.); Interleukin-2; T Cell Growth Factor; TCGF; Aldesleukin; Super-2

After reconstitution: for 10?g size: 0.1mg/ml, for 100?g size: 1mg/ml

32160000

<0.01EU/?g protein (LAL test).

solid

Lyophilized. Contains PBS.

After reconstitution, prepare aliquots and store at -20?C. Avoid freeze/thaw cycles. Centrifuge lyophilized vial before opening and reconstitution. PBS containing at least 0.1% BSA should be used for further dilutions.

Recombinant Protein. The extracellular domain of human IL-2 (aa 21-153) (mutant H9T containing the mutations of H9: L80F / R81D / L85V / I 86V / I92F and the new mutation Q126T) is fused at the C-terminus to the Fc portion of human IgG1 (Knobs-into-Holes technology) (see reference: J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)). Source: HEK 293 cells. Lyophilized. Contains PBS. 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 Superkine (Fc) is an artificial variant of IL-2 called H9, containing mutations at positions L80F / R81D / L85V / I 86V / I92F. These mutations are located in the molecule's core that acts to stabilize the structure and to give it a receptor-binding conformation mimicking native IL-2 bound to CD25. These mutations effectively eliminate the functional requirement of IL-2 for CD25 expression and elicit proliferation of T cells. Compared to IL-2, the IL-2 superkine induces superior expansion of cytotoxic T cells, leading to improved anti-tumor responses in vivo, and elicits proportionally less toxicity by lowering the expansion of T-regulatory cells and reducing pulmonary oedema. A new version of IL-2 Superkine with a new additional mutation called H9T reduces the binding of IL-2Rgamma and promotes the expansion of CD8+ T cells without driving terminal differentiation. TCR-transgenic and chimeric antigen receptor-modified CD8+ T cells that are expanded with H9T showed stronger anti-tumor activity in vivo in mouse models of melanoma and acute lymphoblastic leukemia. The new variant of IL-2 called H9T, helps to maintain activated CD8+ T cells in a stem-cell-like state, with greater anti-tumor activity in two mouse models. Like IL-2 Superkine (H9), IL-2 Superkine (H9T) also works on human T cells. The protein IL-2 Superkine H9T (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-2 Superkine H9T: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 Superkine H9T (monomeric):Fc-KIH (human) (rec.).

~45kDa and 28kDa (SDS-PAGE)

Uniprot link P60568 : IL-2 (human) http://www.uniprot.org/uniprot/P60568 AfCS Signaling Gateway link A006222: IL-2 (mouse) http://www.signaling-gateway.org/molecule/query?afcsid=A006222

Plastic Vial

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 Superkine (Fc) is an artificial variant of IL-2 called H9, containing mutations at positions L80F / R81D / L85V / I 86V / I92F. These mutations are located in the molecule's core that acts to stabilize the structure and to give it a receptor-binding conformation mimicking native IL-2 bound to CD25. These mutations effectively eliminate the functional requirement of IL-2 for CD25 expression and elicit proliferation of T cells. Compared to IL-2, the IL-2 superkine induces superior expansion of cytotoxic T cells, leading to improved anti-tumor responses in vivo, and elicits proportionally less toxicity by lowering the expansion of T-regulatory cells and reducing pulmonary oedema. A new version of IL-2 Superkine with a new additional mutation called H9T reduces the binding of IL-2Rgamma and promotes the expansion of CD8+ T cells without driving terminal differentiation. TCR-transgenic and chimeric antigen receptor-modified CD8+ T cells that are expanded with H9T showed stronger anti-tumor activity in vivo in mouse models of melanoma and acute lymphoblastic leukemia. The new variant of IL-2 called H9T, helps to maintain activated CD8+ T cells in a stem-cell-like state, with greater anti-tumor activity in two mouse models. Like IL-2 Superkine (H9), IL-2 Superkine (H9T) also works on human T cells. The protein IL-2 Superkine H9T (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-2 Superkine H9T: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 Superkine H9T (monomeric):Fc-KIH (human) (rec.).

>95% (SDS-PAGE)

The extracellular domain of human IL-2 (aa 21-153) (mutant H9T containing the mutations of H9: L80F / R81D / L85V / I 86V / I92F and the new mutation Q126T) is fused at the C-terminus to the Fc portion of human IgG1 (Knobs-into-Holes technology) (see reference: J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)).

HEK 293 cells

Binds to human and mouse IL-2R.

Fc

Non-hazardous

Interleukins

41116127

Stable for at least 6 months after receipt when stored at -20?C. Working aliquots are stable for up to 3 months when stored at -20?C.