Adalimumab (Anti-Human TNF-alpha, Human Antibody) is one of the leading therapies for the treatment of rheumatoid arthritis. It is a humanized monoclonal antibody that binds to TNF-α and blocks its interaction with the TNF receptor [1]. It neutralizes both soluble as well as transmembrane TNF-α[2].
Adalimumab (Anti-Human TNF-alpha, Human Antibody) prevents major inflammatory effects of TNF-α on endothelial activation, endothelial monocyte adhesion, endothelial leakage[3].
Adalimumab (Anti-Human TNF-alpha, Human Antibody) prevented TNFα upregulation, reduced photoreceptor cell death, slowed microglial and Müller cell activation, improved antioxidant response and ameliorated the energetic and metabolic dysfunction at P18[4]. VaD rats treated with Adalimumab (Anti-Human TNF-alpha, Human Antibody) exhibited significant improvements in memory. In addition, Adalimumab (Anti-Human TNF-alpha, Human Antibody) treatment significantly alleviated neuronal loss in the hippocampi of VaD rats[5]. The important role of TNF-α for atherosclerotic plaque development in experimental models is well documented, different TNF-α-deficient mice models consistently showed reduced plaque burden[6,7]. Adalimumab (Anti-Human TNF-alpha, Human Antibody) has demonstrated a good prognosis and improvement of physical function in rheumatoid arthritis [8].
参考文献:
[1]. Hürlimann D, Forster A, et,al. Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis. Circulation. 2002 Oct 22;106(17):2184-7. doi: 10.1161/01.cir.0000037521.71373.44. PMID: 12390945.
[2]. Ternant D, Ducourau E, et,al. Pharmacokinetics and concentration-effect relationship of adalimumab in rheumatoid arthritis. Br J Clin Pharmacol. 2015 Feb;79(2):286-97. doi: 10.1111/bcp.12509. PMID: 25223394; PMCID: PMC4309634.
[3]. Oberoi R, Schuett J, et,al. Targeting Tumor Necrosis Factor-α with Adalimumab: Effects on Endothelial Activation and Monocyte Adhesion. PLoS One. 2016 Jul 28;11(7):e0160145. doi: 10.1371/journal.pone.0160145. PMID: 27467817; PMCID: PMC4965117.
[4]. Martínez-Fernández de la Cámara C, Hernández-Pinto AM, et,al. Adalimumab Reduces Photoreceptor Cell Death in A Mouse Model of Retinal Degeneration. Sci Rep. 2015 Jul 14;5:11764. doi: 10.1038/srep11764. PMID: 26170250; PMCID: PMC4501000.
[5]. Xu JJ, Guo S, et,al. Adalimumab ameliorates memory impairments and neuroinflammation in chronic cerebral hypoperfusion rats. Aging (Albany NY). 2021 May 24;13(10):14001-14014. doi: 10.18632/aging.203009. Epub 2021 May 24. PMID: 34030135; PMCID: PMC8202885.
[6]. Br?nén L, Hovgaard L, et,al. Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol. 2004 Nov;24(11):2137-42. doi: 10.1161/01.ATV.0000143933.20616.1b. Epub 2004 Sep 2. PMID: 15345516.
[7]. Ohta H, Wada H, et,al. Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice. Atherosclerosis. 2005 May;180(1):11-7. doi: 10.1016/j.atherosclerosis.2004.11.016. Epub 2005 Jan 20. PMID: 15823270.
[8]. Toussirot E, Wendling D. The use of TNF-alpha blocking agents in rheumatoid arthritis: an update. Expert Opin Pharmacother. 2007 Sep;8(13):2089-107. doi: 10.1517/14656566.8.13.2089. PMID: 17714062.
阿达木单抗（抗人 TNF-α，人抗体）是治疗类风湿性关节炎的主要疗法之一。它是一种与 TNF-α 结合的人源化单克隆抗体；并阻断其与 TNF 受体 [1] 的相互作用。它中和可溶性和跨膜 TNF-α；[2]。
阿达木单抗（抗人 TNF-α，人抗体）可预防 TNF-α 的主要炎症作用;对内皮活化、内皮单核细胞粘附、内皮渗漏的影响[3]。
阿达木单抗（抗人 TNF-α，人抗体）可预防 TNFα；上调、减少光感受器细胞死亡、减缓小胶质细胞和 Müller 细胞活化、改善抗氧化反应并改善 P18[4] 的能量和代谢功能障碍。用阿达木单抗（抗人 TNF-α，人抗体）治疗的 VaD 大鼠在记忆力方面表现出显着改善。此外，阿达木单抗（抗人 TNF-α，人抗体）治疗显着减轻了 VaD 大鼠海马的神经元丢失[5]。 TNF-α的重要作用；对于实验模型中动脉粥样硬化斑块的发展，有据可查，不同的 TNF-α-缺陷小鼠模型始终显示斑块负荷减少 [6,7]。阿达木单抗（抗人 TNF-α，人抗体）在类风湿性关节炎中表现出良好的预后和身体机能的改善 [8]。
| Pharmacokinetic experiment [1]: | |
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Preparation Method |
Using double-antigen enzyme-linked immunosorbent TNF-|á Adalimumab -coated plates and their detection by peroxidase-conjugated IgG. |
|
Reaction Conditions |
These patients received 40 mg adalimumab subcutaneously every other week combined with methotrexate and follow-up was done for 1 year. |
|
Applications |
Thirty patients treated for RA were analysed. The following pharmacokinetic and PK-PD parameters were estimated (interidividual coefficient of variation): apparent volume of distribution (Vd /F) = 10.8 l (92%); apparent clearance (CL/F) = 0.32 l day(-1) (17%); first-order absorption rate (ka ) = 0.28 day(-1) ; CRP input (kin ) = 22.0 mg l(-1) day(-1) (65%); adalimumab concentration leading to a 50% decrease in kin (C50 ) = 3.6 mg l(-1) (88%); baseline DAS28 (DAS0 ) = 5.5 mg l(-1) (11%); and adalimumab concentration leading to 50% decrease of DAS0 (IC50 ) = 11.0 mg l(-1) (71%). Simulations showed that a 160 mg loading dose should reduce the time to reach efficacy in terms of both CRP and DAS28 after the first injection. |
| Cell experiment [2]: | |
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Cell lines |
THP-1 monocytes |
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Preparation Method |
CellTracker green-labelled THP-1 monocytes on a HUVECs monolayer after incubation with conditioned media from oxLDL-stimulated THP-1 macrophages (oxLDL CM) with or without adalimumab (ada) for 4 hours followed by the addition of CellTracker green-labelled THP-1 monocytes. |
|
Reaction Conditions |
1 |?/mL Adalimumab (Anti-Human TNF-alpha, Human Antibody) for 4 hours |
|
Applications |
The TNF-|á inhibitor adalimumab suppresses adhesion of THP-1 monocytes to endothelial cells. |
| Animal experiment [3]: | |
|
Animal models |
Rd10 mice |
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Preparation Method |
To evaluate the effect of Adalimumab (Anti-Human TNF-alpha, Human Antibody), each rd10 mouse received one intraperitoneal injection of Adalimumab (Anti-Human TNF-alpha, Human Antibody) aline solution at 3 mg/kg every three days starting at P9 and until P17. |
|
Dosage form |
3 mg/kg Adalimumab (Anti-Human TNF-alpha, Human Antibody)every three days |
|
Applications |
intraperitoneal administration of Adalimumab (Anti-Human TNF-alpha, Human Antibody) significantly decreased the number of TUNEL-positive cells in the ONL at P18 (2.7??à?0.4 TUNEL-positive cells) compared to vehicle-treated rd10 retinas (12.5??à?2.4 TUNEL-positive cells) |
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参考文献: [1]. Ternant D, Ducourau E, et,al. Pharmacokinetics and concentration-effect relationship of adalimumab in rheumatoid arthritis. Br J Clin Pharmacol. 2015 Feb;79(2):286-97. doi: 10.1111/bcp.12509. PMID: 25223394; PMCID: PMC4309634. [2]. Oberoi R, Schuett J, et,al. Targeting Tumor Necrosis Factor-|á with Adalimumab: Effects on Endothelial Activation and Monocyte Adhesion. PLoS One. 2016 Jul 28;11(7):e0160145. doi: 10.1371/journal.pone.0160145. PMID: 27467817; PMCID: PMC4965117. [3].Mart¨anez-Fern¨￠ndez de la C¨￠mara C, Hern¨￠ndez-Pinto AM, et,al. Adalimumab Reduces Photoreceptor Cell Death in A Mouse Model of Retinal Degeneration. Sci Rep. 2015 Jul 14;5:11764. doi: 10.1038/srep11764. PMID: 26170250; PMCID: PMC4501000. |
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