He Xuzhi, Cruz Jazmina L, Joseph Shannon, Pett Nicola, Chew Hui Yi, Tuong Zewen K, Okano Satomi, Kelly Gabrielle, Veitch Margaret, Simpson Fiona, Wells James W
The University of Queensland Diamantina Institute, Faculty of Medicine, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
Queensland Head and Neck Cancer Centre, Princess Alexandra Hospital, Brisbane, QLD, Australia.
Oncotarget. 2018 Jan 13;9(15):12250-12260. doi: 10.18632/oncotarget.24242. eCollection 2018 Feb 23.
The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer. However, only 15-20% patients benefit from this drug, thus new strategies to improve cetuximab efficiency are required. We aimed to develop a reliable and easy preclinical mouse model to evaluate the efficacy of EGFR-targeted antibodies and examine the immune mechanisms involved in tumour regression. We selected an anti-mouse EGFR mAb, 7A7, which has been reported to be "mouse cetuximab" and to exhibit similar properties to its human counterpart. Unfortunately, we were unable to reproduce previous results obtained with the 7A7 mAb. In our hands, 7A7 failed to recognize mouse EGFR, both in native and reducing conditions. Moreover, administration of 7A7 in an EGFR-expressing HPV38 tumour model did not have any impact on tumour regression or animal survival. We conclude that 7A7 does not recognize mouse EGFR and therefore cannot be used as the mouse equivalent of cetuximab use in humans. As a number of groups have spent effort and resources with similar issues we feel that publication is a responsible approach.
表皮生长因子受体（EGFR）在许多肿瘤表面选择性表达，如非小细胞肺癌、卵巢癌、结直肠癌和头颈癌。因此，EGFR已成为癌症治疗的靶点。西妥昔单抗是一种人/鼠嵌合单克隆抗体（mAb），可与EGFR结合，在该过程中它既能抑制信号传导，又能通过抗体依赖性细胞介导的细胞毒性（ADCC）诱导细胞死亡。西妥昔单抗已被批准用于治疗头颈鳞状细胞癌（HNSCC）和结直肠癌患者。然而，只有15%-20%的患者能从这种药物中获益，因此需要新的策略来提高西妥昔单抗的疗效。我们旨在建立一种可靠且简便的临床前小鼠模型，以评估EGFR靶向抗体的疗效，并研究肿瘤消退所涉及的免疫机制。我们选择了一种抗小鼠EGFR单克隆抗体7A7，该抗体已被报道为“小鼠西妥昔单抗”，并表现出与其人源对应物相似的特性。不幸的是，我们无法重现先前用7A7单克隆抗体获得的结果。在我们的实验中，7A7在天然和还原条件下均无法识别小鼠EGFR。此外，在表达EGFR的HPV38肿瘤模型中给予7A7对肿瘤消退或动物存活没有任何影响。我们得出结论，7A7不能识别小鼠EGFR，因此不能用作人类西妥昔单抗的小鼠等效物。由于许多研究团队都在类似问题上投入了精力和资源，我们认为发表这一结果是一种负责任的做法。
