AdipoGen推出的InVivoKines系列重組蛋白，是新一代重組融合蛋白，用于免疫治療、臨床前和體內轉化研究。InVivoKines系列蛋白是基于Fc的融合蛋白，采用KIH（Knobs-into-Holes）技術生產。

Silenced Fc-KIH Domain (LALA-PG Mutations)

AdipoGen利用hIgG1-P329G LALA突變設計了其沉默的Fc-KIH結構域，完-全消除了FcγR和C1q相互作用，并且與FcRn相互作用和Fc穩(wěn)定性不受影響。LALA-PG突變未顯示出與Fcγ受體或C1q的結合，在基于功能細胞的檢測中無活性，并且不引起炎性細胞因子反應。

圖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是維持和擴增效應T細胞（CD4和CD8）、調節(jié)性T細胞（Tregs）和自然殺傷（NK）細胞所需的關鍵淋巴細胞生長因子。IL-2通過包含IL-2Rβ和IL-2Rγ的中等親和力受體和包含IL-2rα（CD25）的高親和力受體發(fā)出信號。IL-2對T細胞的活化和增殖至關重要，通常用于TIL細胞治療以促進T細胞擴增。

研究顯示IL-2超因子誘導T細胞（CD4/CD8）增殖（非T reg）會導致細胞毒性CD8 T細胞和NK細胞的擴增，因此與人IL-2 WT相比改善了體內抗腫瘤反應。IL-2 Superkine (monomeric):Fc-KIH比IL-2 Superkine:Fc (dimeric)更有效，與金標準IL-2 Aldesleukin的效果相當或更好。

圖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).

圖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由兩個亞單位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具有針對多種病毒的有效抗病毒活性和通過產生抗血管生成趨化因子的抗腫瘤活性。IL-27 (mouse):Fc-KIH (human) (rec.)是一種異二聚體Fc-KIH蛋白，與小鼠和人IL-27R復合物結合并激活小鼠和人細胞中Stat3磷酸化。與其他品牌的經典二聚體IL-27 (mouse):Fc相比，其活性更強。

圖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).

圖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，包括食欲調節(jié)、對代謝、妊娠、細胞存活、免疫反應和炎癥的作用。AdipoGen的同型二聚體蛋白Fc (LALA-PG)-KIH (human):GDF15 (mouse) (rec.)是一種用于體內研究的具有長效高活性的獨-特蛋白質。它形成具有生物活性的同型二聚體，不同于其他形成無活性大聚集體的經典GDF15-Fc蛋白。

圖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系列重組蛋白產品列表

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