Fresolimumab
(Synonyms: 非苏木单抗,GC1008) 目录号 : GC65539
Fresolimumab是一种高亲和力的人源化单克隆抗体，能够结合并抑制蛋白转化生长因子β（TGFβ）的所有亚型。Fresolimumab对TGFβ1、TGFβ2和TGFβ3的Kd值分别为1.7±0.6nM、3.0±1.2nM、2.0±1.2nM。
Cas No.:948564-73-6
Sample solution is provided at 25 µL, 10mM.
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Fresolimumab is a high-affinity humanized monoclonal antibody that binds to and inhibits all isoforms of the protein transforming growth factor β (TGFβ)[1]. The Kd values of Fresolimumab for TGFβ1, TGFβ2, and TGFβ3 are 1.7±0.6nM, 3.0±1.2nM, and 2.0±1.2nM, respectively[2]. Fresolimumab can treat idiopathic pulmonary fibrosis (IPF), focal segmental glomerulosclerosis, and cancer[3, 4].
In vitro, treatment of esophageal adenocarcinoma OE19 and 031M cells with Fresolimumab (10μg/mL) for 1 week reversed the mesenchymal morphology of the cells and reduced the expression of the mesenchymal marker VIM[5]. Fresolimumab (12.5, 50nM) treated MC38, EMT6 and HCT116 cells expressing human TGFβRII blocked TGFβ1-induced SMAD2/3 phosphorylation[6].
In vivo, Fresolimumab (10, 25, 50mg/kg) treated mice with human colon cancer Lovo cell xenografts by intraperitoneal injection significantly reduced TGFβ levels in tumors[6].
References:
[1] Lacouture M E, Morris J C, Lawrence D P, et al. Cutaneous keratoacanthomas/squamous cell carcinomas associated with neutralization of transforming growth factor β by the monoclonal antibody fresolimumab (GC1008)[J]. Cancer Immunology, Immunotherapy, 2015, 64: 437-446.
[2] Moulin A, Mathieu M, Lawrence C, et al. Structures of a pan‐specific antagonist antibody complexed to different isoforms of TGFβ reveal structural plasticity of antibody–antigen interactions[J]. Protein Science, 2014, 23(12): 1698-1707.
[3] Trachtman H, Goyal S, Finn P, et al. Neutralizing TGF-β in fibrotic renal disorders: focus on fresolimumab[J]. Drugs Future, 2012, 37(787): 10.1358.
[4] Vincenti F, Fervenza F C, Campbell K N, et al. A phase 2, double-blind, placebo-controlled, randomized study of fresolimumab in patients with steroid-resistant primary focal segmental glomerulosclerosis[J]. Kidney international reports, 2017, 2(5): 800-810.
[5] Steins A, Ebbing E A, Creemers A, et al. Chemoradiation induces epithelial‐to‐mesenchymal transition in esophageal adenocarcinoma[J]. International journal of cancer, 2019, 145(10): 2792-2803.
[6] Greco R, Qu H, Qu H, et al. Pan-TGFβ inhibition by SAR439459 relieves immunosuppression and improves antitumor efficacy of PD-1 blockade[J]. Oncoimmunology, 2020, 9(1): 1811605.
Fresolimumab是一种高亲和力的人源化单克隆抗体，能够结合并抑制蛋白转化生长因子β（TGFβ）的所有亚型[1]。Fresolimumab对TGFβ1、TGFβ2和TGFβ3的Kd值分别为1.7±0.6nM、3.0±1.2nM、2.0±1.2nM[2]。Fresolimumab能够治疗特发性肺纤维化（IPF）、局灶节段性肾小球硬化和癌症[3, 4]。
在体外，Fresolimumab（10μg/mL）处理食管腺癌OE19、031M细胞1周，逆转了细胞的间充质形态，降低了间充质标志物VIM的表达[5]。Fresolimumab（12.5，50nM）处理表达人TGFβRII的小鼠细胞系MC38、EMT6和人HCT116 细胞，阻断了TGFβ1诱导的SMAD2/3磷酸化[6]。
在体内，Fresolimumab（10，25，50mg/kg）通过腹腔注射治疗人结肠癌Lovo细胞异种移植小鼠，显著了降低肿瘤内TGFβ水平[6]。
| Cell experiment [1]: | |
Cell lines | OE19、031M cells |
Preparation Method | OE19 and 031M cells were subjected to chemoradiation for 14 days and Fresolimumab (10μg/mL) was added to the therapy schedule during the last 7 days of chemoradiation. |
Reaction Conditions | 10μg/mL; 7 days |
Applications | Fresolimumab could reverse the mesenchymal morphology of both OE19 and 031M cells, even during chemoradiation. |
| Animal experiment [2]: | |
Animal models | Female athymic nude-NU (NCr)-Foxn1n homozygous (HOM) mice |
Preparation Method | Female athymic nude-NU (NCr)-Foxn1n homozygous (HOM) mice received 5×106 Lovo cells/200μL (s.c.) in the right flank. Mice were pooled and randomized (8-10 mice/group) when tumor size reached approximately 50-90mm3. SAR439459, Fresolimumab (10, 25, 50mg/kg) or HuIgG4 isotype were injected intraperitoneally (i.p.) and tumor growth was measured as described above. Antitumor efficacy was evaluated by tumor volume measurement, and animal body weights assessed. Tumors were measured with a caliper 2-3 times weekly. When a tumor reached approximately 2000mm3 or there was 10% body weight loss or 20% tumor ulceration, animals were euthanized. |
Dosage form | 10, 25, 50mg/kg; i.p. |
Applications | In Lovo model, we compared the ability of SAR439459 and Fresolimumab as a monotherapy to inhibit active TGFβ1 at various doses and observed that treatment with either of these antibodies reduced intratumoral TGFβ levels at all the doses. |
References: | |
| Cas No. | 948564-73-6 | SDF | Download SDF |
| 别名 | 非苏木单抗,GC1008 | ||
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at -80°C | |
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