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(jié)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(fā)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(fā)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(chuàng)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(fā)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(yōu)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(fā) 的Fc融合蛋白
• Fc-KIH技術允許Fc異源二聚體化，創(chuàng)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(wěn)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(fā)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(wěn)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(fā)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(jié)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(yōu)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(jié)、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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