University of Alabama at Birmingham, Department of Surgery, Division of Otolaryngology - Head and Neck Surgery, 1670 University Boulevard, Volker Hall G082, Birmingham, AL 35233, USA.
Oral Oncol. 2013 Oct;49(10):991-7. doi: 10.1016/j.oraloncology.2013.07.006. Epub 2013 Aug 3.
Despite advances in treatment modalities, head and neck squamous cell carcinoma (HNSCC) remains a challenge to treat with poor survival and high morbidity, necessitating a therapy with greater efficacy. EDC22 is an extracellular drug conjugate of the monoclonal antibody targeting CD147 (glycoprotein highly expressed on HNSCC cells) linked with a small drug molecule inhibitor of Na, K-ATPase. In this study, EDC22's potential as a treatment modality for HNSCC was performed.
HNSCC cell lines (FADU, OSC-19, Cal27, SCC-1) were cultured in vitro and proliferation and cell viability were assessed following treatment with a range of concentrations of EDC22 (0.25-5.00μg/mL). Mice bearing HNSCC xenografts (OSC-19, SCC-1) were treated with either EDC22 (3-10mg/kg), anti-CD147 monoclonal antibody, cisplatin (1mg/kg) or radiation therapy (2Gy/week) monotherapy or in combination.
In vitro, treatment with minimal concentration of EDC22 (0.25μg/mL) significantly decreased cellular proliferation and cell viability (p<0.0001). In vivo, systemic treatment with EDC22 significantly decreased primary tumor growth rate in both an orthotopic mouse model (OSC-19) and a flank tumor mouse model (SCC-1) (p<0.05). In addition, EDC22 therapy resulted in a greater reduction in tumor growth in vivo compared to radiation monotherapy (p<0.05) and a similar reduction in tumor growth compared to cisplatin monotherapy. Combination therapy provided no significant further reduction in tumor growth relative to EDC22 monotherapy.
EDC22 is a potent inhibitor of HNSCC cell proliferation in vitro and in vivo, warranting further investigations of its clinical potential in the treatment of HNSCC.
尽管治疗方法有所进步，但头颈部鳞状细胞癌（HNSCC）的治疗仍然具有挑战性，生存率低，发病率高，因此需要更有效的治疗方法。EDC22 是一种靶向 CD147（HNSCC 细胞高表达的糖蛋白）的单克隆抗体的细胞外药物偶联物，与 Na，K-ATPase 的小分子药物抑制剂相连。在这项研究中，研究了 EDC22 作为治疗 HNSCC 的一种方法的潜力。
体外培养 HNSCC 细胞系（FADU、OSC-19、Cal27、SCC-1），并在不同浓度的 EDC22（0.25-5.00μg/mL）处理后评估细胞增殖和细胞活力。用 EDC22（3-10mg/kg）、抗 CD147 单克隆抗体、顺铂（1mg/kg）或放射治疗（每周 2Gy）单药或联合治疗荷有 HNSCC 异种移植瘤的小鼠（OSC-19、SCC-1）。
在体外，用最小浓度的 EDC22（0.25μg/mL）处理可显著降低细胞增殖和细胞活力（p<0.0001）。在体内，全身给予 EDC22 可显著降低荷瘤小鼠（OSC-19）和荷瘤小鼠（SCC-1）的原发性肿瘤生长速度（p<0.05）。此外，EDC22 治疗导致肿瘤生长的体内减少量大于放射治疗单药（p<0.05），与顺铂单药治疗相比，肿瘤生长减少量相似。与 EDC22 单药治疗相比，联合治疗对肿瘤生长没有显著的进一步减少。
EDC22 是体外和体内 HNSCC 细胞增殖的有效抑制剂，值得进一步研究其在治疗 HNSCC 中的临床潜力。
