细胞因子是一类小蛋白，能在细胞间传递信息，具有免疫调节和效应功能，这些作用使得它们在各种免疫相关疾病的临床前和临床研究中极-具吸引力。它们在免疫中发挥关键作用，而基于工程化细胞因子的疗法代表了免疫治疗的新发展。然而细胞因子的广泛应用受到血液半衰期短、多效性和脱靶效应的限制。对细胞因子生物学的深入了解以及创新的细胞因子工程技术可以应对这些限制，但他们通常又无法用于基础研究。
InVivoKines™ 是 AdipoGen Life Sciences利用Knobs-into-Holes (KIH) 技术研发的新一代重组融合蛋白，用于免疫治疗、临床前和转化体内研究。如需订购Adipogen公司产品，请联系国内授权代理欣博盛生物。
| InVivoKines™ 优势与特点： | |
| • 具有天然构象——在HEK293或CHO细胞中生产 |
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| • 在无动物条件下生产 | |
| • 通过ELISA及基于细胞的检测测试的高生物活性 | |
| • 通过SEC验证的纯度和均一性 | |
| • 低内毒素水平 | |
| • 批次间一致性 | |
天然细胞因子与Fc融合(KIH技术)
InVivoKines™ 是使用 Knobs-into-Holes (KIH) 技术研发 的Fc融合蛋白
• Fc-KIH技术允许Fc异源二聚体化，创造出具有两个不同臂的结构，以设计天然存在的活性单体、异源二聚体或同源二聚体蛋白
• Fc-KIH 域增强了细胞因子的血浆半衰期，从而在保持活性的同时显著改善药代动力学(PK)
• Fc-KIH 域与 Fcγ受体(FcγRs)和补体 C1q结合，可能导致抗体依赖性细胞介导的细胞毒性作用(ADCC)、抗体依赖性细胞介导的吞噬作用(ADCP)和补体依赖的细胞毒性作用(CDC)
• Fc-KIH LALA-PG突变抑制了与FcγRs和C1q的结合，而与FcRn结合和Fc稳定性不受影响
• Fc-KIH 在内毒素含量低的哺乳动物细胞中生产
• Fc-KIH 蛋白是为体内研开的，但也同样适用于体外实验！
AdipoGen Life Sciences利用KIH技术开发单体、异源二聚体或同源二聚体Fc融合蛋白.
沉默的Fc-KIH域(LALA-PG 突变)
AdipoGen Life Sciences利用hIgG1-P329G LALA突变来设计其沉默的Fc-KIH域，这些突变完-全消除了与FcγR和C1q的相互作用，包含了有限数量的突变，并且不影响FcRn的相互作用和 Fc 的稳定性。LALA-PG突变显示未检测到与Fc受体或 C1q 的结合，在基于功能细胞的检测中无活性，并且不引发炎症性细胞因子反应。
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LITERATURE: • (1) Knobs-into-Holes (KIH) Technology: J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996) • (2) Efficient Generation of Bispecific Murine Antibodies for Pre-Clinical Investigations in Syngeneic Rodent Models: A.F. Labrijn, et al.; Sci. Rep. 7, 2476 (2017) • (3) Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions:T. Schlothauer, et al.; Prot. Eng. Design Sel. 29, 457 (2016) |
单体IL-2蛋白
IL-2 Superkine已被证明能诱导 T 细胞(CD4/CD8)增殖(非 T 调节细胞)，导致细胞毒性CD8 T细胞和NK细胞的显著扩增，因此，与人IL-2 WT相比，体内抗肿瘤反应得到改善。IL-2 Superkine(单体):Fc-KIH比IL-2 Superkine:Fc(二聚体)更高效，等同于或优于金标准 IL-2 Aldesleukin。
| IL-2 Superkine (monomeric): Fc-KIH (human)(rec.) |
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| AG-40B-0222 | 10μg|3x10μg|100μg | |
| NEWIL-2 Superkine H9T (monomeric): Fc-KIH(human) (rec.) | ||
| AG-40B-0223 | 10μg|3x10μg|100μg | |
| IL-2 (human) (monomeric): Fc-KIH (human) (rec.) | ||
| AG-40B-0224 | 10μg|3x10μg|100μg | |
| IL-2 (mouse) (monomeric): Fc-KIH (human) (rec.) | ||
| AG-40B-0225 | 10μg|3x10μg|100μg | |
| FIGURE: IL-2 Superkine (monomeric):Fc-KIH (human) (rec.) (Prod. No. AG-40B-0222)activates the IL-2 receptor better than the dimeric IL-2 Superkine ((Prod. No. AG40B-0111) using the IL-2 Bioass ay (Promega JA2201). | ||
NEW IL-27 (mouse):Fc-KIH (human) (rec.) AG-40B-0236
IL-27由两个亚基IL-27p28和EBI3组成。它促进NK和T细胞增殖以及 IFN-γ 的产生。IL-27对多种病毒具有强大的抗病毒活性，并通过产生抗血管生成趋化因子具有抗肿瘤活性。 IL-27 (mouse):Fc-KIH (human) (rec.)是一种异源二聚体Fc-KIH结构体，与小鼠和人的IL-27R复合物结合，激活小鼠和人细胞中Stat3磷酸化。与传统的二聚体IL-277 (mouse):Fc相比，其活性更强。 |
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| FIGURE: IL-27 (mouse):Fc-KIH (human) (rec.) (Prod. N o.AG-40B-0236) (Heterodimer)is more active than an IL-27 (mouse):Fc from a competitor (Dimer of Heterodimer)in Stat 3 phosphorylation in HepG2 cells (shown as quantification figure of the westernblot) | ||
NEW Fc (LALA-PG)-KIH (human):GDF15 (mouse) (rec.) AG-40B-0245
GDF15的作用是多方面的，包括对食欲调节、代谢、妊娠、细胞存活、免疫反应和炎症的作用。 AdipoGen Life Sciences的Fc (LALAPG)-KIH(human):GDF15(mouse) (rec.)是一种在体内研究中具有长效高活性的独-特蛋白质，与其他形成无活性大聚集体的经典GDF15-Fc蛋白不同，是具有生物活性的同源二聚体。 |
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| FIGURE: A binding assay shows that Fc (LALA-PG)-KIH (human):GDF15 (mouse) (rec.) (Prod. No. AG-40B-0245) binds with high affinity to its receptor GFRAL (mouse). The Fc (LALA-PG)-KIH(human):GDF15 (mouse) (rec.), which migrates as a dimer by SEC, binds to its receptor mouse GFRAL with an EC50 ~15 ng/ml, while the GDF15 (mouse):Fc (human) (rec.), that migrates asan aggregate by SEC (>1000 kDa), binds similar to the control protein with low affinity. | ||
InVivoKines™−产品目录
| 产品名称 | 货号 | 结构 | Fc-KIH 默认 |
| IL-2 (human) (monomeric): Fc-KIH (human) (rec.) | AG-40B-0224 | Monomer | No |
| IL-2 (mouse) (monomeric): Fc-KIH (human) (rec.) | AG-40B-0225 | Monomer | No |
| IL-2 Superkine (monomeric): Fc-KIH (human) (rec.) | AG-40B-0222 | Monomer | No |
| IL-2 Superkine H9T (monomeric): Fc-KIH (human) (rec.) | AG-40B-0223 | Monomer | No |
| IL-2 (human) (Switch-2) (monomeric): Fc-KIH (human) (rec.) | AG-40B-0234 | Monomer | No |
| IL-7 (human) (monomeric): Fc-KIH (human) (rec.) | AG-40B-0238 | Monomer | No |
| IL-7 (human) (monomeric): Fc (LALA-PG)-KIH (human) (rec.) NEW | AG-40B-0247 | Monomer | LALA-PG |
| IL-12 (mouse): Fc-KIH (human) (rec.) | AG-40B-0240 | Heterodimer | No |
| IL-21 (mouse) (monomeric): Fc (LALA-PG)-KIH (human) (rec.) NEW | AG-40B-0250 | Monomer | LALA-PG |
| IL-23 (mouse): Fc-KIH (human) (rec.) | AG-40B-0235 | Heterodimer | No |
| IL-23 (mouse): Fc (LALA-PG)-KIH (human) (rec.) NEW | AG-40B-0248 | Heterodimer | LALA-PG |
| IL-27 (mouse): Fc-KIH (human) (rec.) | AG-40B-0236 | Heterodimer | No |
| IL-27 (mouse): Fc (LALA-PG)-KIH (human) (rec.) NEW | AG-40B-0249 | Heterodimer | LALA-PG |
| IL-33 (oxidation resistant) (human) (monomeric): Fc-KIH (human) (rec.) | AG-40B-0233 | Monomer | No |
| IL-37 (human) (monomeric): Fc-KIH (human) (rec.) | AG-40B-0221 | Monomer | No |
| IL-38 (aa 1-152) (human) (monomeric): Fc-KIH (human) (rec.) | AG-40B-0241 | Monomer | No |
| IL-38 (aa 20-152) (human) (monomeric): Fc-KIH (human) (rec.) | AG-40B-0226 | Monomer | No |
| IL-38 (aa 3-152) (mouse) (monomeric): Fc-KIH (human) (rec.) | AG-40B-0227 | Monomer | No |
| Fc (LALA-PG)-KIH (human): GDF15 (mouse) (rec.) NEW | AG-40B-0245 | Homodimer | LALA-PG |
| Fc (LALA-PG)-KIH (human): Irisin (monomeric) (rec.) NEW | AG-40B-0246 | Monomer | LALA-PG |
| Fc-KIH (human) IgG1 Control (rec.) | AG-35B-0015 | Control | No |
| Fc (LALA-PG)-KIH (human) IgG1 Control (rec.) | AG-35B-0018 | Control | LALA-PG |
InVivoKines™ —可选结构
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