Faculty of Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
Oral Oncol. 2020 Jul;106:104689. doi: 10.1016/j.oraloncology.2020.104689. Epub 2020 Apr 21.
Squamous cell carcinoma of head and neck (SCCHN) is the fifth most prevalent cancer worldwide. Because the anatomical complexity of this region, complete surgical resection is often not achievable and conventional chemotherapy would aid locoregional control and mitigate distant metastasis. Nonetheless, the nonspecific cytotoxicity and short in vivo half-life of conventional chemotherapeutic drugs limit their effects. Given the high frequency of overexpression of wild type epidermal growth factor receptor (EGFR), we exploit EGFR as a homing beacon for drug delivery system with cytotoxic payloads.
We generated fully human anti-EGFR single chain variable fragment (scFv)-conjugated immunoliposomes (IL) containing doxorubicin and vinorelbine and tested their anti-neoplastic efficacy in vitro and in vivo.
Our IL enhanced endocytosis and significantly reduced the half maximal inhibitory concentrations of the therapeutic payloads when compared to non-targeting liposomal counterparts in various cell lines of SCCHN. Furthermore, median survival time was significantly prolonged in subcutaneous and orthotopic SCCHN xenograft murine models treated with our IL formulations than those treated with non-targeting counterparts (94 days versus 60 days and 72 days versus 56 days, respectively) without evident increased systemic toxicity.
The therapeutic index of the chemotherapeutic payloads was augmented by our EFGR-targeting IL formulation and they are warranted for further development and preclinical trial.
头颈部鳞状细胞癌（SCCHN）是全球第五大常见癌症。由于该区域解剖结构复杂，通常无法实现完全手术切除，而传统化疗有助于局部区域控制并减轻远处转移。然而，传统化疗药物的非特异性细胞毒性和体内半衰期短限制了其效果。鉴于野生型表皮生长因子受体（EGFR）的高表达频率，我们将 EGFR 作为含有细胞毒性有效载荷的药物递送系统的归巢信标加以利用。
我们生成了完全人源抗 EGFR 单链可变片段（scFv）-缀合的载多柔比星和长春瑞滨免疫脂质体（IL），并在体外和体内测试了它们的抗肿瘤功效。
与非靶向脂质体相比，我们的 IL 在各种 SCCHN 细胞系中增强了内吞作用，并显著降低了治疗有效载荷的半最大抑制浓度。此外，与接受非靶向 IL 治疗的小鼠相比，接受我们的 IL 制剂治疗的皮下和原位 SCCHN 异种移植小鼠模型的中位生存时间显著延长（分别为 94 天与 60 天和 72 天与 56 天），而没有明显增加全身毒性。
我们的 EGFR 靶向 IL 制剂增强了化疗有效载荷的治疗指数，值得进一步开发和临床前试验。
