Complement-mediated immunotherapy to the Oral Squamous Cell Carcinoma with Cetuximab

为了保护口腔区域的形态和功能，需要有效和选择性的抗口腔癌药物。我们的重点是西妥昔单抗，这是用于治疗表皮生长因子受体(EGFR)表达的癌症患者。西妥昔单抗和人血清孵育后，HSC4细胞表面的补体沉积(C3)略有增加。另一方面，肿瘤细胞上表达的补体抑制物阻碍了某些单抗的治疗效果。我们研究了一种在肿瘤细胞上放大补体激活并压倒补体抑制功能的策略。在CR2-Fc存在的情况下，西妥昔单抗和人血清孵育的HSC4细胞的补体沉积和裂解增强。CR2-Fc提高了抗体治疗的疗效，在抗体浓度有限或肿瘤抗原密度较低的情况下可能会提供特殊的益处。

To conserve both form and function in the oral area, effective and selective drugs against oral cancer will be required. We focused on Cetuximab, that is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing cancer. Complement deposition (C3) on HSC4 (human oral squamous cell carcinomas cell line) by incubation with Cetuximab and human serum was slightly enhanced. On the other hands, complement inhibitors expressed on tumor cells provide a hindrance to the therapeutic efficacy of some monoclonal antibodies. We investigated a strategy to amplify complement activation on tumor cells and overwhelm complement inhibitor function. Complement deposition and lysis of HSC4 cells by incubation with Cetuximab and human serum was enhanced in the presence of CR2-Fc. CR2-Fc enhances the therapeutic efficacy of antibody therapy and may provide particular benefits under conditions of limiting antibody concentration or low tumor antigen density.