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  • Cetuximab (C225)
Cetuximab (C225)的可视化放大

Cetuximab (C225)

Cetuximab (C225) (C225) 是一种人 IgG1 单克隆抗体,可抑制表皮生长因子受体 (EGFR),SPR 对 EGFR 的 Kd 为 0.201 nM。西妥昔单抗 (C225) 具有有效的抗肿瘤活性。

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  • 货号: ajce52676
  • CAS: 205923-56-4
  • 别名: 西妥昔单抗; C225
  • 分子式: C6484H10042N1732O2023S36
  • 分子量: 145543.35
  • 纯度: >98%
  • 溶解度:
  • 储存: Store at 4°C, do not freeze
  • 库存: 现货

Background

Cetuximab is a chimeric monoclonal antibody generated from fusion of the variable region of the murine anti-EGFR monoclonal antibody M225 and the human IgG1 constant region. It produced antibody retains high affinity and specificity to EGFR and reduces immunogenicity.[1] Cetuximab bound with high affinity to FcγRI (EC50 = 0.13 nM) and FcγRIIIa (EC50 = 6 nM). It effectively induced ADCC across multiple tumor cell lines.[4] Treatment with 100?μg/ml cetuximab for 24h enhances the cytotoxicity effect of RSL3 treatment on KRAS mutant CRC cells.[2]


In vitro experiment indicated it that radiation enhances cetuximab (0.5 μg/ml)-mediated ADCC and activation of NK cells.[3] Treatment with 20 μg/mL cetuximab inhibited the proliferation of the parental UMSCC1 cell line (UMSCC1-P) ,while the three HNSCC cetuximab-resistant clones (C2, C5, and C11) were completely refractory to cetuximab.[6]


In vivo experiment it shown that cetuximab (13?mg/kg, s.c.) enhances the inhibitory effects of RSL3 and RSL3-induced ferroptosis.[2] In vivo, after i.v. injection of 4 doses of 10 mg/kg body-weight demonstrated that cetuximab markly inhibited tumor growth in SCC1 tumor bearing mice.[5] In vivo experiment it illustrated that cetuximab-treated (50 mg/kg, i.p.) tumors showed delayed growth, when mice were inoculated with the NSCLC H226 cell line individually with 2x106 tumor cells in the dorsal flank.[6]

参考文献:
[1]. Xiong HQ, et al. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial. J Clin Oncol. 2004 Jul 1;22(13):2610-6.
[2]. Yang J, et al. Cetuximab promotes RSL3-induced ferroptosis by suppressing the Nrf2/HO-1 signalling pathway in KRAS mutant colorectal cancer. Cell Death Dis. 2021 Nov 13;12(11):1079.
[3]. Jin WJ, et al. Tumor-Specific Antibody, Cetuximab, Enhances the In Situ Vaccine Effect of Radiation in Immunologically Cold Head and Neck Squamous Cell Carcinoma. Front Immunol. 2020 Nov 12;11:591139.
[4]. Patel D, et al. IgG isotype, glycosylation, and EGFR expression determine the induction of antibody-dependent cellular cytotoxicity in vitro by cetuximab. Hum Antibodies. 2010;19(4):89-99.
[5]. Niu G, et al. Cetuximab-based immunotherapy and radioimmunotherapy of head and neck squamous cell carcinoma. Clin Cancer Res. 2010 Apr 1;16(7):2095-105.
[6]. Iida M, et al. Targeting the HER Family with Pan-HER Effectively Overcomes Resistance to Cetuximab. Mol Cancer Ther. 2016 Sep;15(9):2175-86.


西妥昔单抗是一种嵌合单克隆抗体,由鼠类抗 EGFR 单克隆抗体 M225 的可变区和人 IgG1 恒定区融合而成。它产生的抗体对 EGFR 保持高亲和力和特异性并降低免疫原性。[1] Cetuximab 以高亲和力结合 FcγRI (EC50 = 0.13 nM) 和 FcγRIIIa (EC50 = 6 nM)。它有效地诱导多种肿瘤细胞系的ADCC。[4]用100μg/ml西妥昔单抗处理24h增强了RSL3处理对KRAS突变CRC细胞的细胞毒性作用。[2]


体外实验表明,辐射增强了西妥昔单抗(0.5 μg/ml)介导的ADCC和NK细胞的活化。[3]用20 μg/mL西妥昔单抗治疗抑制了亲本细胞的增殖UMSCC1细胞系(UMSCC1-P),而三个HNSCC西妥昔单抗耐药克隆(C2、C5和C11)对西妥昔单抗完全耐药。[6]


体内实验表明,西妥昔单抗 (13mg/kg, s.c.) 增强了 RSL3 和 RSL3 诱导的铁死亡的抑制作用。[2] 在体内,静脉注射后。注射4次10 mg/kg体重的西妥昔单抗表明西妥昔单抗显着抑制SCC1荷瘤小鼠的肿瘤生长。[5] 体内实验表明西妥昔单抗处理(50 mg/kg, i.p.) 肿瘤显示延迟生长,当小鼠单独接种 NSCLC H226 细胞系时,在背侧有 2x106 个肿瘤细胞。[6]

Protocol

Cell experiment [1]:

Cell lines

SCC1 and UM-SCC-22B cells

Preparation Method

The toxicity of cetuximab to SCC1 and UM-SCC-22B cells was determined by MTT assay. At 72 h or 120 h after treatment with different doses of cetuximab (ranging from 0.1 nM to 0.5 μM), the culture medium was replaced and 50 μl of 1.0 mg/ml sterile filtered 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT; Sigma) was added to each well.

Reaction Conditions

0.1 nM to 0.5 μM at 72 h or 120 h

Applications

Treatment with cetuximab produced only modest inhibition of cell proliferation on SCC1 cells in vitro as determined by MMT assay.

Animal experiment [2]:

Animal models

BALB/c (nu/nu) female nude mice

Preparation Method

Xenografts were established in female nude mice (BALB c[nu/nu]) by subcutaneous injection of head and neck squamous cell carcinoma cell lines a UT-SCC-14 and b UT-SCC-2. Cetuximab (1?mg/injection) was administered by intraperitoneal injection at day 10, 13 and 16. The tumour size was recorded at an interval of 2–3 days, n?=?10-14.

Dosage form

1?mg, i.p.

Applications

Cetuximab treatment showed reduction in the nuclear accumulation of HIF-1α, while the overall HIF-1α expression was not significantly altered. And after cetuximab treatment a downregulation of CAIX was only found in UT-SCC-14 xenografts. Cetuximab treatment affects the tumour growth and the tumour partial oxygen pressure as measured by LiPc EPR oximetry.

参考文献:

[1]. Niu G, et al. Cetuximab-based immunotherapy and radioimmunotherapy of head and neck squamous cell carcinoma. Clin Cancer Res. 2010 Apr 1;16(7):2095-105.


[2]. Gustafsson H, et al. EPR Oximetry of Cetuximab-Treated Head-and-Neck Tumours in a Mouse Model. Cell Biochem Biophys. 2017 Dec;75(3-4):299-309.

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