García-Foncillas Jesús, Sunakawa Yu, Aderka Dan, Wainberg Zev, Ronga Philippe, Witzler Pauline, Stintzing Sebastian
Cancer Institute, University Hospital Fundacion Jimenez Diaz, Autonomous University of Madrid, Madrid, Spain.
Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.
Front Oncol. 2019 Sep 20;9:849. doi: 10.3389/fonc.2019.00849. eCollection 2019.
Cetuximab and panitumumab are two distinct monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR), and both are widely used in combination with chemotherapy or as monotherapy to treat patients with wild-type metastatic colorectal cancer. Although often considered interchangeable, the two antibodies have different molecular structures and can behave differently in clinically relevant ways. More specifically, as an immunoglobulin (Ig) G1 isotype mAb, cetuximab can elicit immune functions such as antibody-dependent cell-mediated cytotoxicity involving natural killer cells, T-cell recruitment to the tumor, and T-cell priming via dendritic cell maturation. Panitumumab, an IgG2 isotype mAb, does not possess these immune functions. Furthermore, the two antibodies have different binding sites on the EGFR, as evidenced by mutations on the extracellular domain that can confer resistance to one of the two therapeutics or to both. We consider a comparison of the properties of these two antibodies to represent a gap in the literature. We therefore compiled a detailed, evidence-based educational review of the known molecular, clinical, and functional differences between the two antibodies and concluded that they are distinct therapeutic agents that should be considered individually during treatment planning. Available data for one agent can only partly be extrapolated to the other. Looking to the future, the known immune activity of cetuximab may provide a rationale for this antibody as a combination partner with investigational chemotherapy plus immunotherapy regimens for colorectal cancer.
西妥昔单抗和帕尼单抗是两种针对表皮生长因子受体（EGFR）的不同单克隆抗体（mAb），二者都广泛用于与化疗联合或作为单药治疗野生型转移性结直肠癌患者。尽管这两种抗体常被认为可互换使用，但它们具有不同的分子结构，在临床相关方面的表现也有所不同。更具体地说，作为一种免疫球蛋白（Ig）G1亚型单克隆抗体，西妥昔单抗可引发免疫功能，如涉及自然杀伤细胞的抗体依赖性细胞介导的细胞毒性、T细胞募集至肿瘤以及通过树突状细胞成熟引发T细胞致敏。帕尼单抗是一种IgG2亚型单克隆抗体，不具备这些免疫功能。此外，这两种抗体在EGFR上具有不同的结合位点，细胞外结构域的突变可证明这一点，这些突变可导致对这两种治疗药物之一或两者产生耐药性。我们认为对这两种抗体的特性进行比较在文献中存在空白。因此，我们对这两种抗体之间已知的分子、临床和功能差异进行了详细的、基于证据的教育性综述，并得出结论：它们是不同的治疗药物，在治疗规划过程中应分别予以考虑。一种药物的现有数据只能部分外推至另一种药物。展望未来，西妥昔单抗已知的免疫活性可能为该抗体作为结直肠癌研究性化疗加免疫治疗方案的联合用药提供理论依据。
