Development of Anti-EGFR scFv-mediated Drug Delivery Systems for Targeted Therapy of Head and Neck Squamous Cell Carcinoma
Date Issued
2016
Date
2016
Author(s)
Chung, Meng-Jhe
Abstract
Epidermal growth factor receptor, a member of the ErbB family, has been reported to involve in pathogenesis and progression in a plethora of cancer types. Genetic aberration of EGFR such as activating mutation and amplification are implicated in about 30% of all epithelial cancers including head and neck squamous cell carcinoma (HNSCC). Therefore, it is rational and promising to develop a targeted regimen toward this receptor. Previous work of our laboratory acquired two novel scFvs that could specifically bind to EGFR extracellular domains (EGFR-Ex) through phage display technique. Conjugation of these two scFvs to liposome enhanced binding and internalization ability compared to non-targeting counterpart in cell lines of liver, lung and head and neck cancer cells. Furthermore, EGFR scFv-conjugated liposomal doxorubicin or vinorelbine could augment their cytotoxic effects on cancer cells. The specificity and binding ability of EGFR scFv were also verified through in vivo homing assay. In the FaDu-derived subcutaneous xenograft model, EGFR scFv-conjugated liposomal drugs reduced the tumor burden more efficiently and increased the survival rates than non-targeting liposomal drugs. Taken together, these results reveal the potential benefit of EGFR-specific scFv in respect of therapeutic enhancement of targeted drug delivery in the treatment of head and neck cancer.
Subjects
head and neck cancer
EGFR
scFv
drug delivery systems
SDGs
Type
thesis