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(nèi)轉(zhuǎn)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(shù)生產(chǎn)。

Silenced Fc-KIH Domain (LALA-PG Mutations)

AdipoGen利用hIgG1-P329G LALA突變設(shè)計了其沉默的Fc-KIH結(jié)構(gòu)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(jié)合，在基于功能細(xì)胞的檢測中無活性，并且不引起炎性細(xì)胞因子反應(yīng)。

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(yīng)T細(xì)胞（CD4和CD8）、調(diào)節(jié)性T細(xì)胞（Tregs）和自然殺傷（NK）細(xì)胞所需的關(guān)鍵淋巴細(xì)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(xì)胞的活化和增殖至關(guān)重要，通常用于TIL細(xì)胞治療以促進T細(xì)胞擴增。

研究顯示IL-2超因子誘導(dǎo)T細(xì)胞（CD4/CD8）增殖（非T reg）會導(dǎo)致細(xì)胞毒性CD8 T細(xì)胞和NK細(xì)胞的擴增，因此與人IL-2 WT相比改善了體內(nèi)抗腫瘤反應(yīng)。IL-2 Superkine (monomeric):Fc-KIH比IL-2 Superkine:Fc (dimeric)更有效，與金標(biāo)準(zhǔn)IL-2 Aldesleukin的效果相當(dāng)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(xì)胞增殖以及IFN-γ的產(chǎn)生。IL-27具有針對多種病毒的有效抗病毒活性和通過產(chǎn)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(fù)合物結(jié)合并激活小鼠和人細(xì)胞中Stat3磷酸化。與其他品牌的經(jīng)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(diào)節(jié)、對代謝、妊娠、細(xì)胞存活、免疫反應(yīng)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(nèi)研究的具有長效高活性的獨-特蛋白質(zhì)。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(jīng)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(chǎn)品列表

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