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英夫利昔单抗,一种完全人源化单克隆抗体,靶向表皮生长因子受体细胞外结构域III

In-Labeled panitumumab, a fully human monoclonal antibody directed against the extracellular domain III of the epidermal growth factor receptor

作者信息

Chopra Arvind

机构信息

National Center for Biotechnology Information, NLM, Bethesda, MD 20894

PMID:22741180
Abstract

Panitumumab is a fully human anti-epidermal factor receptor (EGFR) monoclonal antibody (mAb) that has been approved by the United States Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancers that express the EGFR and are unresponsive to chemotherapy (1). This mAb has a very high affinity for the extracellular domain III of the EGFR. The general characteristics of panitumumab have been described by Argiles et al. (2), and its mode of action has been illustrated by Dubois and Cohen (1). The fully human mAb has been reported to be well tolerated by individuals, slows disease progression, and improves the progression-free survival of patients (3). Therefore, [In]-labeled panitumumab ([In]-panitumumab) was evaluated for the noninvasive detection of EGFR-positive tumors in an effort to screen for patients who would benefit from radioimmunotherapy with this mAb after it was labeled with a suitable radionuclide (3). The In-labeled mAb was studied , and the biodistribution of [In]-panitumumab was investigated in athymic mice bearing xenograft tumors generated with A431, HT-29, LS-174T, SHAW (obtained from the National Cancer Institute), and SKOV-3 cell lines, respectively (3). In addition, gamma scintigraphic images were acquired from mice bearing xenograft tumors to confirm noninvasive visualization of the lesions.

摘要

帕尼单抗是一种全人源抗表皮生长因子受体(EGFR)单克隆抗体(mAb),已获美国食品药品监督管理局(FDA)批准,用于治疗表达EGFR且对化疗无反应的转移性结直肠癌(1)。该单克隆抗体对EGFR的细胞外结构域III具有非常高的亲和力。帕尼单抗的一般特性已由阿吉莱斯等人描述(2),其作用方式已由杜布瓦和科恩阐明(1)。据报道,这种全人源单克隆抗体个体耐受性良好,可减缓疾病进展,并提高患者的无进展生存期(3)。因此,对[铟]-标记的帕尼单抗([铟]-帕尼单抗)进行了评估,以用于EGFR阳性肿瘤的无创检测,以便筛选出在用合适的放射性核素标记该单克隆抗体后可从放射免疫治疗中获益的患者(3)。对铟标记的单克隆抗体进行了研究,并分别在携带由A431、HT - 29、LS - 174T、SHAW(从美国国立癌症研究所获得)和SKOV - 3细胞系产生的异种移植肿瘤的无胸腺小鼠中研究了[铟]-帕尼单抗的生物分布(3)。此外,从携带异种移植肿瘤的小鼠获取了γ闪烁显像图像,以确认病变的无创可视化。