A novel extracellular drug conjugate significantly inhibits head and neck squamous cell carcinoma.
A novel extracellular drug conjugate significantly inhibits head and neck squamous cell carcinoma.
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DOI：
10.1016/j.oraloncology.2013.07.006
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发表时间：
2013-10
期刊：
影响因子：
4.8
通讯作者：
Rosenthal, Eben L.
中科院分区：
文献类型：
--
作者：
Sweeny, Larissa;Hartman, Yolanda E.;Zinn, Kurt R.;Prudent, James R.;Marshall, David J.;Shekhani, Mohammed S.;Rosenthal, Eben L.
尽管在治疗方式上取得了进展，但头颈部鳞状细胞癌（HNSCC）仍然是一个治疗挑战，生存率低，发病率高，需要更有效的治疗。EDC 22是靶向CD 147（HNSCC细胞上高度表达的糖蛋白）的单克隆抗体与Na，K-ATP酶小分子药物抑制剂连接的细胞外药物偶联物。在这项研究中，EDC 22作为HNSCC的治疗方式的潜力进行。体外培养HNSCC细胞系（FADU、OSC-19、Cal 27、SCC-1），并在用一系列浓度的EDC 22（0.25-5.00 μg/mL）处理后评估增殖和细胞活力。携带HNSCC异种移植物（OSC-19，SCC-1）的小鼠用EDC 22（3-10 mg/kg）、抗-CD 147单克隆抗体、顺铂（1 mg/kg）或放射疗法（2戈伊/周）单药治疗或组合治疗。在体外，用最小浓度的EDC 22（0.25 μg/mL）处理显著降低细胞增殖和细胞活力（p < 0.0001）。在体内，在原位小鼠模型（OSC-19）和侧腹肿瘤小鼠模型（SCC-1）中，用EDC 22的全身性治疗显著降低原发性肿瘤生长速率（p < 0.05）。此外，与放射单一疗法相比，EDC 22疗法导致体内肿瘤生长的更大降低（p < 0.05），并且与顺铂单一疗法相比，肿瘤生长的类似降低。相对于EDC 22单一疗法，联合疗法没有提供肿瘤生长的显著进一步减少。EDC 22是体外和体内HNSCC细胞增殖的有效抑制剂，促进了对其治疗HNSCC的临床潜力的进一步研究。
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 (0.25–5.00 μg/mL). Mice bearing HNSCC xenografts (OSC-19, SCC-1) were treated with either EDC22 (3–10 mg/kg), anti-CD147 monoclonal antibody, cisplatin (1 mg/kg) or radiation therapy (2 Gy/week) monotherapy or in combination. In vitro, treatment with minimal concentration of EDC22 (0.25 μg/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.
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影响因子：
--
作者：
Newman, J. Robert;Bohannon, Isaac A.;Zhang, Wenyue;Skipper, Joni B.;Grizzle, William E.;Rosenthal, Eben L.
通讯作者：
Rosenthal, Eben L.
影响因子：
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5.6
作者：
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6.2
作者：
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Urashima, M