Garrido Greta, Sanchez Belinda, Rodriguez Hilda Maria, Lorenzano Pablo, Alonso Daniel, Fernandez Luis Enrique
Vaccines' Department, Center of Molecular Immunology, Havana, Cuba.
Hybrid Hybridomics. 2004 Jun;23(3):168-75. doi: 10.1089/1536859041224280.
The epidermal growth factor receptor (EGFR) is highly expressed in many types of epithelial tumors. EGFR overexpression has been associated with an advanced stage of the disease, with resistance to standard therapies, and, for certain tumors, with poor patient prognosis. As a result, EGFR has been considered a meaningful target in anti-tumor strategies. Active and passive immunotherapies blocking EGFR and its ligands have been explored. But for successful pre-clinical evaluation of these approaches, well-established murine tumor models are not available and highly desirable. We described, for the first time, the generation and characterization of an anti-murine EGFR extracellular domain monoclonal antibody (7A7 MAb) (IgG1). 7A7 was generated by immunization of Balb/c mice with the recombinant extracellular domain of murine EGFR (rECD-mEGFR). 7A7 recognized an epitope present in the amino acidic core of the antigen and is cross-reactive with the human EGFR. Interestingly, this MAb was able to specifically bind EGFR at the cell surface, allowing the assessment of its differential expression in a panel of murine cells. Noteworthy, in a preliminary immunohistochemical study with 7A7 MAb, recognition of Balb/c mice skin sections and EGFR-positive tumors were observed. We concluded that 7A7 MAb is a valuable tool for EGFR-based therapeutic pre-clinical studies.
表皮生长因子受体(EGFR)在多种上皮肿瘤中高表达。EGFR过表达与疾病的晚期阶段、对标准疗法的耐药性相关,并且对于某些肿瘤而言,还与患者预后不良有关。因此,EGFR被认为是抗肿瘤策略中有意义的靶点。阻断EGFR及其配体的主动和被动免疫疗法已得到探索。但要对这些方法进行成功的临床前评估,目前还没有且非常需要成熟的小鼠肿瘤模型。我们首次描述了一种抗小鼠EGFR胞外域单克隆抗体(7A7单克隆抗体)(IgG1)的产生及特性。7A7是通过用小鼠EGFR的重组胞外域(rECD-mEGFR)免疫Balb/c小鼠产生的。7A7识别抗原氨基酸核心中存在的一个表位,并且与人EGFR具有交叉反应性。有趣的是,这种单克隆抗体能够在细胞表面特异性结合EGFR,从而能够评估其在一组小鼠细胞中的差异表达。值得注意的是,在一项用7A7单克隆抗体进行的初步免疫组织化学研究中,观察到了对Balb/c小鼠皮肤切片和EGFR阳性肿瘤的识别。我们得出结论,7A7单克隆抗体是基于EGFR的治疗性临床前研究的宝贵工具。