AdipoGen推出的InVivoKines系列重组蛋白，是新一代重组融合蛋白，用于免疫治疗、临床前和体内转化研究。InVivoKines系列蛋白是基于Fc的融合蛋白，采用KIH（Knobs-into-Holes）技术生产。
Silenced Fc-KIH Domain (LALA-PG Mutations)
AdipoGen利用hIgG1-P329G LALA突变设计了其沉默的Fc-KIH结构域，完全消除了FcγR和C1q相互作用，并且与FcRn相互作用和Fc稳定性不受影响。LALA-PG突变未显示出与Fcγ受体或C1q的结合，在基于功能细胞的检测中无活性，并且不引起炎性细胞因子反应。
图1. Fc (LALA-PG)-KIH (human) IgG1 Control (rec.) (Prod. No. AG-35B-0018) does not bind to the human Fcγ Receptor I.
Monomeric IL-2 Proteins
IL-2是维持和扩增效应T细胞（CD4和CD8）、调节性T细胞（Tregs）和自然杀伤（NK）细胞所需的关键淋巴细胞生长因子。IL-2通过包含IL-2Rβ和IL-2Rγ的中等亲和力受体和包含IL-2rα（CD25）的高亲和力受体发出信号。IL-2对T细胞的活化和增殖至关重要，通常用于TIL细胞治疗以促进T细胞扩增。
研究显示IL-2超因子诱导T细胞（CD4/CD8）增殖（非T reg）会导致细胞毒性CD8 T细胞和NK细胞的扩增，因此与人IL-2 WT相比改善了体内抗肿瘤反应。IL-2 Superkine (monomeric):Fc-KIH比IL-2 Superkine:Fc (dimeric)更有效，与金标准IL-2 Aldesleukin的效果相当或更好。
图2. 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. AG-40B-0111) using the IL-2 Bioassay (Promega JA2201).
图3. IL-2 Superkine (monomeric):Fc-KIH (human) (rec.) (Prod. No. AG-40B-0222) and IL-2 (human) (monomeric):Fc-KIH (human) (rec.) (Prod. No. AG-40B-0224) are equivalent or better than the Gold Standard IL-2 Aldesleukin to increase proliferation of CTLL-2 cytotoxic T cells.
高活性Heterodimeric IL-27-KIH Protein
IL-27由两个亚单位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具有针对多种病毒的有效抗病毒活性和通过产生抗血管生成趋化因子的抗肿瘤活性。IL-27 (mouse):Fc-KIH (human) (rec.)是一种异二聚体Fc-KIH蛋白，与小鼠和人IL-27R复合物结合并激活小鼠和人细胞中Stat3磷酸化。与其他品牌的经典二聚体IL-27 (mouse):Fc相比，其活性更强。
图6. L-27 (mouse):Fc-KIH (human) (rec.) (Prod. No. AG-40B-0236) (Heterodimer) is more active than an IL-27 (mouse):Fc from a competitor (Dimer of Heterodimer) in Stat3 phosphorylation in HepG2 cells (shown as quantification figure of the western blot).
图7. IL-27 (mouse):Fc-KIH (human) (rec.) (Prod. No. AG-40B-0236) (Heterodimer) is more active than an IL-27 (mouse):Fc from a competitor (Dimer of Heterodimer) in Stat3 phosphorylation in HepG2 cells.
高活性Homodimeric GDF15-KIH Protein
GDF15的作用是多效的，包括食欲调节、对代谢、妊娠、细胞存活、免疫反应和炎症的作用。AdipoGen的同型二聚体蛋白Fc (LALA-PG)-KIH (human):GDF15 (mouse) (rec.)是一种用于体内研究的具有长效高活性的独特蛋白质。它形成具有生物活性的同型二聚体，不同于其他形成无活性大聚集体的经典GDF15-Fc蛋白。
图8. 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 as an aggregate by SEC (>1000 kDa), binds similar to the control protein with low affinity.
AdipoGen目前InVivoKines系列重组蛋白产品列表
产品名称 | 货号 | Protein Construct | Fc-KIH Silenced |
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) (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 (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.) | 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.) | 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.) | 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.) | 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.) | AG-40B-0245 | Heterodimer | LALA-PG |
Fc (LALA-PG)-KIH (human):Irisin (monomeric) (rec.) | 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 |
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