細胞因子是一類小蛋白，能在細胞間傳遞信息，具有免疫調節和效應功能，這些作用使得它們在各種免疫相關疾病的臨床前和臨床研究中極-具吸引力。它們在免疫中發揮關鍵作用，而基于工程化細胞因子的療法代表了免疫治療的新發展。然而細胞因子的廣泛應用受到血液半衰期短、多效性和脫靶效應的限制。對細胞因子生物學的深入了解以及創新的細胞因子工程技術可以應對這些限制，但他們通常又無法用于基礎研究。
InVivoKines™ 是 AdipoGen Life Sciences利用Knobs-into-Holes (KIH) 技術研發的新一代重組融合蛋白，用于免疫治療、臨床前和轉化體內研究。如需訂購Adipogen公司產品，請聯系國內授權代理欣博盛生物。
| InVivoKines™ 優勢與特點： | |
| • 具有天然構象——在HEK293或CHO細胞中生產 |
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| • 在無動物條件下生產 | |
| • 通過ELISA及基于細胞的檢測測試的高生物活性 | |
| • 通過SEC驗證的純度和均一性 | |
| • 低內毒素水平 | |
| • 批次間一致性 | |
天然細胞因子與Fc融合(KIH技術)
InVivoKines™ 是使用 Knobs-into-Holes (KIH) 技術研發 的Fc融合蛋白
• Fc-KIH技術允許Fc異源二聚體化，創造出具有兩個不同臂的結構，以設計天然存在的活性單體、異源二聚體或同源二聚體蛋白
• Fc-KIH 域增強了細胞因子的血漿半衰期，從而在保持活性的同時顯著改善藥代動力學(PK)
• Fc-KIH 域與 Fcγ受體(FcγRs)和補體 C1q結合，可能導致抗體依賴性細胞介導的細胞毒性作用(ADCC)、抗體依賴性細胞介導的吞噬作用(ADCP)和補體依賴的細胞毒性作用(CDC)
• Fc-KIH LALA-PG突變抑制了與FcγRs和C1q的結合，而與FcRn結合和Fc穩定性不受影響
• Fc-KIH 在內毒素含量低的哺乳動物細胞中生產
• Fc-KIH 蛋白是為體內研開的，但也同樣適用于體外實驗！
AdipoGen Life Sciences利用KIH技術開發單體、異源二聚體或同源二聚體Fc融合蛋白.
沉默的Fc-KIH域(LALA-PG 突變)
AdipoGen Life Sciences利用hIgG1-P329G LALA突變來設計其沉默的Fc-KIH域，這些突變完-全消除了與FcγR和C1q的相互作用，包含了有限數量的突變，并且不影響FcRn的相互作用和 Fc 的穩定性。LALA-PG突變顯示未檢測到與Fc受體或 C1q 的結合，在基于功能細胞的檢測中無活性，并且不引發炎癥性細胞因子反應。
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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) |
單體IL-2蛋白
IL-2 Superkine已被證明能誘導 T 細胞(CD4/CD8)增殖(非 T 調節細胞)，導致細胞毒性CD8 T細胞和NK細胞的顯著擴增，因此，與人IL-2 WT相比，體內抗腫瘤反應得到改善。IL-2 Superkine(單體):Fc-KIH比IL-2 Superkine:Fc(二聚體)更高效，等同于或優于金標準 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由兩個亞基IL-27p28和EBI3組成。它促進NK和T細胞增殖以及 IFN-γ 的產生。IL-27對多種病毒具有強大的抗病毒活性，并通過產生抗血管生成趨化因子具有抗腫瘤活性。 IL-27 (mouse):Fc-KIH (human) (rec.)是一種異源二聚體Fc-KIH結構體，與小鼠和人的IL-27R復合物結合，激活小鼠和人細胞中Stat3磷酸化。與傳統的二聚體IL-277 (mouse):Fc相比，其活性更強。 |
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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，包括對食欲調節、代謝、妊娠、細胞存活、免疫反應和炎癥的作用。 AdipoGen Life Sciences的Fc (LALAPG)-KIH(human):GDF15(mouse) (rec.)是一種在體內研究中具有長效高活性的獨-特蛋白質，與其他形成無活性大聚集體的經典GDF15-Fc蛋白不同，是具有生物活性的同源二聚體。 |
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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™?產品目錄
| 產品名稱 | 貨號 | 結構 | Fc-KIH 默認 |
| 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™ —可選結構
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