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AdipoGen InVivoKines系列重組蛋白

2024-04-02
瀏覽次數(shù): 40

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)。

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Silenced Fc-KIH Domain (LALA-PG Mutations)

AdipoGen利用hIgG1-P329G LALA突變?cè)O(shè)計(jì)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(cè)中無(wú)活性,并且不引起炎性細(xì)胞因子反應(yīng)。

 AdipoGen InVivoKines系列重組蛋白?

圖1. Fc (LALA-PG)-KIH (human) IgG1 Control (rec.) (Prod. No. AG-35B-0018) does not bind to the human Fcγ?Receptor I.

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Monomeric IL-2 Proteins

IL-2是維持和擴(kuò)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(zhǎng)因子。IL-2通過(guò)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(hào)。IL-2對(duì)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(jìn)T細(xì)胞擴(kuò)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(huì)導(dǎo)致細(xì)胞毒性CD8 T細(xì)胞和NK細(xì)胞的擴(kuò)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。

 AdipoGen InVivoKines系列重組蛋白

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).


 AdipoGen InVivoKines系列重組蛋白

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.

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高活性Heterodimeric IL-27-KIH Protein

IL-27由兩個(gè)亞單位IL-27p28和EBI3組成。它促進(jìn)NK和T細(xì)胞增殖以及IFN-γ的產(chǎn)生。IL-27具有針對(duì)多種病毒的有效抗病毒活性和通過(guò)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(qiáng)。

 AdipoGen InVivoKines系列重組蛋白

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).


 AdipoGen InVivoKines系列重組蛋白

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.

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高活性Homodimeric GDF15-KIH Protein

GDF15的作用是多效的,包括食欲調(diào)節(jié)、對(duì)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(zhǎng)效高活性的獨(dú)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(wú)活性大聚集體的經(jīng)典GDF15-Fc蛋白。

 AdipoGen InVivoKines系列重組蛋白

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.

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 AdipoGen InVivoKines系列重組蛋白

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AdipoGen目前InVivoKines系列重組蛋白產(chǎn)品列表

產(chǎn)品名稱

貨號(hào)

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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