Isthmin-1 (mouse) (rec.) (His) Reference: AG-40B-0215 Isthmin-1 (ISM1) was first identified as a gene expressed in the Xenopus midbrain hind brain organizer called isthmus, with a proposed role during early brain development. Isthmin-1 encodes a predicted ~50-kDa protein containing a signal peptide, a thrombospondin domain and an adhesion-associated domain. Isthmin-1 is important for embryonic and postnatal development. Growing evidence has shown that aberrant expression of Isthmin-1 can also affect the biological behavior of cancer. The Ism1 gene is conserved in mice and humans. A recent study showed that Ism1 is an adipokine that induces glucose uptake in human and mouse adipocytes. Ism1 is secreted by mature adipocytes and triggers a signaling cascade similar to that of insulin, regulating glucose uptake while suppressing lipid accumulation. Recombinant Isthmin-1 or overexpression of Ism1 causes a robust increase in GLUT4-dependent glucose uptake in cultured primary murine and immortalized human adipocytes as well as in primary human muscle cells and prevents insulin resistance and hepatic steatosis in a diet-induced obesity mouse model. Ablation of Isthmin-1 causes glucose intolerance and impaired insulin-stimulated adipocyte glucose uptake. Isthmin-1 suppresses de novo lipogenesis and increases protein synthesis in hepatocytes whereas Isthmin-1 knockdown in adipocytes reduces glucose uptake and insulin-dependent phosphorylation of protein kinase AKT at serine residue 473 (p-AKTSer473). Isthmin-1 signaling is dependent on PI3K and shares downstream phosphorylation targets with insulin signaling, such as p-AKTSer473, p-AKTThr308, p-ERK1/2Thr202/Tyr204 and p-S6Ser235/236. Isthmin-1 does not seem to act through the insulin receptor or the insulin-like growth factor 1 receptor; it is most likely to signal through another, yet to be identified, receptor tyrosine kinase.
TAPBPL (mouse):Fc (human) (rec.) Reference: AG-40B-0216 T cells play critical roles in the adaptive immune system, protecting the human body against cancer, bacterial, viral, fungal, and parasitic infections. T cell immune response is tightly controlled by immune checkpoint proteins that negatively or positively regulate T cell response. Among the immune checkpoint proteins, the B7 family plays a key role in controlling immune responses and belongs to the immunoglobulin (Ig) superfamily. A number of B7 family ligands have been identified, such as B7-1 (CD80), B7-2 (CD86), PD-L1 (B7-H1), PD-L2 (B7-DC), B7-H2 [inducible T cell co-stimulator ligand (ICOS)], B7-H3, B7-H4 (B7x, B7S1), B7-H5 (VISTA) and B7- H6. Because of the potential clinical applications of immune checkpoint proteins, there has been intense interest in identifying additional T-cell regulators. Recently, new antigen processing (TAP) binding protein-like (TAPBPL)/TAP binding protein-related (TAPBPR) molecule has been shown to share significant sequence similarity with some known B7 family members. TAPBPL protein is expressed on the surface of T cells, on antigen-presenting cells (APCs) including resting B cells, monocytes, macrophages, and DCs, as well as on some cancer cells including leukemia cells. TAPBPL behaves like other immune checkpoint proteins such as B7-H5 / VISTA or PD-L1 with a soluble recombinant version TAPBPL-Fc fusion protein that inhibits the proliferation and activation of CD4 and CD8 T cells in vitro and ameliorates autoimmune disease EAE in vivo. In contrast, treatment with anti-TAPBPL blocking antibody enhances antitumor immunity and inhibits tumor growth in vivo. Therefore, TAPBPL contains typical features of B7 family members, suggesting that it is a B7 family member or a B7 family-related molecule.
TAPBPL (human):Fc (human) (rec.) Reference: AG-40B-0217 T cells play critical roles in the adaptive immune system, protecting the human body against cancer, bacterial, viral, fungal and parasitic infections. T cell immune response is tightly controlled by immune checkpoint proteins that negatively or positively regulate T cell response. Among the immune checkpoint proteins, the B7 family plays a key role in controlling immune responses and belongs to the immunoglobulin (Ig) superfamily. A number of B7 family ligands have been identified, such as B7-1 (CD80), B7-2 (CD86), PD-L1 (B7-H1), PD-L2 (B7-DC), B7-H2 [inducible T cell co-stimulator ligand (ICOS)], B7-H3, B7-H4 (B7x, B7S1), B7-H5 (VISTA) and B7- H6. Because of the potential clinical applications of immune checkpoint proteins, there has been intense interest in identifying additional T-cell regulators. Recently, new antigen processing (TAP) binding protein-like (TAPBPL)/TAP binding protein-related (TAPBPR) molecule has been shown to share significant sequence similarity with some known B7 family members. TAPBPL protein is expressed on the surface of T cells, on antigen-presenting cells (APCs) including resting B cells, monocytes, macrophages, and DCs, as well as on some cancer cells including leukemia cells. TAPBPL behaves like other immune checkpoint proteins such as B7-H5 / VISTA or PD-L1 with a soluble recombinant version TAPBPL-Fc fusion protein that inhibits the proliferation and activation of CD4 and CD8 T cells in vitro and ameliorates autoimmune disease EAE in vivo. In contrast, treatment with anti-TAPBPL blocking antibody enhances antitumor immunity and inhibits tumor growth in vivo. Therefore, TAPBPL contains typical features of B7 family members, suggesting that it is a B7 family member or a B7 family-related molecule.
IL-2 Superkine (Fc) (H9T) Reference: AG-40B-0219 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) should also work on human T cells.
SARS-CoV-2 Spike Protein S1 (RBD):Fc (human) (rec.) (B.1.1.529 Variant, Omicron) Reference: AG-40B-0220 SARS-CoV-2 shares 79.5% sequence identity with SARS-CoV and is 96.2% identical at the genome level to the bat coronavirus BatCoV RaTG133, suggesting it had originated in bats. The coronaviral genome encodes four major structural proteins: the Spike (S) protein, Nucleocapsid (N) protein, Membrane/Matrix (M) protein and the Envelope (E) protein. The SARS Envelope (E) protein contains a short palindromic transmembrane helical hairpin that seems to deform lipid bilayers, which may explain its role in viral budding and virion envelope morphogenesis. The SARS Membrane/Matrix (M) protein is one of the major structural viral proteins. It is an integral membrane protein involved in the budding of the viral particles and interacts with SARS Spike (S) protein and the Nucleocapsid (N) protein. The N protein contains two domains, both of them bind the virus RNA genome via different mechanisms. The CoV Spike (S) protein assembles as trimer and plays the most important role in viral attachment, fusion and entry. It is composed of a short intracellular tail, a transmembrane anchor and a large ectodomain that consists of a receptor binding S1 subunit (RBD domain) and a membrane-fusing S2 subunit. The S1 subunit contains a receptor binding domain (RBD), which binds to the cell surface receptor angiotensin-converting enzyme 2 (ACE2) present at the surface of epithelial cells. The B.1.1.529 variant, called Omicron was first reported to WHO from South Africa on 24 November 2021. Since then, B.1.1.529 has been detected globally. This variant seems to be at least equally infectious than B.1.617.2 (Delta), has already caused super spreader events and has outcompeted Delta within weeks in most countries. B.1.1.529 hosts an unprecedented number of mutations in its spike gene and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness.
GPX1 (human) (rec.) (His) Reference: AG-40A-0150Y Glutathione peroxidase 1 (GPX1) is an antioxidant enzyme that is down-regulated in cancer cells. Protects the hemoglobin in erythrocytes from oxidative breakdown. Its main role is the prevention of cancer initiation by ROS-mediated DNA damage.
Fc-KIH (human) IgG1 Control (rec.) Reference: AG-35B-0015 Negative control in experiments with recombinant proteins fused to human IgG1 Fc-KIH (Knobs-into-Holes) (e.g. Prod. No. AG-40B-0221). This protein is not an appropriate negative control for other standard Fc protein constructs. The protein Fc-KIH (human) IgG1 Control (rec.) is produced by using two different vectors, one encoding for the Fc Knobs sequence with a small linker (synthesizing a protein of 29kDa) 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 Fc-KIH (human) IgG1 Control (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.
IL-2 (human) Superkine H9T (monomeric):Fc-KIH (human) (rec.) Reference: AG-40B-0223 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.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.
IL-2 Superkine (monomeric):Fc-KIH (human) (rec.) Reference: AG-40B-0222 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. The protein IL-2 Superkine (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-2 Superkine: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 Superkine (monomeric):Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.
IL-2 (human) (monomeric):Fc-KIH (human) (rec.) Reference: AG-40B-0224 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.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.
IL-2 (mouse) (monomeric):Fc-KIH (human) (rec.) Reference: AG-40B-0225 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 (mouse) (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-2 (mouse):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 (mouse) (monomeric):Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.
IL-38 (aa 20-152) (human) (monomeric):Fc-KIH (human) (rec.) Reference: AG-40B-0226 IL-38 (IL-1F10) belongs to the IL-1 family of proteins. IL-38 is expressed in heart, placenta, fetal liver, spleen, thymus and tonsil. The expression in a variety of immune tissues and similarity to IL-1Ra suggest a role of IL-38 in the inflammatory response. It has been reported that removal of the N-terminus domain of the interleukins of the IL-1F family such as IL-1F5 / 6 / 8 or 9 (also called IL-36Ra, IL-36alpha, IL-36beta or IL-36gamma) is important to increase their biological activity. Recently it has been shown that IL-38 is N-terminally processed and secreted by apoptotic cells. Released processed IL-38 (20-152) binds to the receptor Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1; TIGIRR-2) at the surface of macrophages. Processed IL-38-activated IL1RAPL1 reduces the production of IL-6 leading to inflammation attenuation. IL-38 is unregulated during some autoimmune diseases such as Systemic Lupus Erythematosus. The protein IL-38 (human) (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-38 (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-38 (human)(monomeric):Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.