Targeted EpCAM-binding for the development of potent and effective anticancer proteins
|Corresponding Author||Ho，Chun Loong|
Protein-based cancer therapies are considered an alternative to conventional anticancer regimens, providing multifunctional properties while showing low toxicity. However, its widespread use is limited by absorption and instability issues, resulting in higher dosage requirements and a prolonged onset of bioactivity to elicit the desired response. Here, we developed a non-invasive antitumor treatment using designed ankyrin repeat protein (DARPin)-anticancer protein-conjugate that specifically targets the cancer biomarker, epithelial cell adhesion molecule (EpCAM). The DARPin-anticancer proteins bind to EpCAM-positive cancer cells and improve the in vitro anticancer efficacy by over 100-folds within 24 h, where the DARPin-tagged human lactoferrin fragment (drtHLF4) IC50 value is within the nanomolar range. Orally administered drtHLF4 was readily absorbed into the systemic flow of the HT-29 cancer murine model, exerting its anticancer effect on other tumors in the host body. Orally administered drtHFL4 cleared HT29-colorectal tumors using a single dose, whereas intratumoral injection cleared HT29-subcutaneous tumors within three doses. This approach addresses the limitations of other protein-based anticancer treatments by providing a non-invasive anticancer therapy with improved potency and tumor-specificity.
First ; Corresponding
Shenzhen Special Fund for Innovation and Entrepreneurship of Overseas High-level Talents Peacock Team[KQTD20170810111314625] ; Shenzhen Institutes of Advanced Technology External Funds[DWKF20190001] ; National Natural Science Foundation of China's Research Fund for International Young Scientists ; Guangdong Innovative and Entrepreneurial Research Team Program[2019ZT08Y191]
|WOS Research Area|
Research & Experimental Medicine ; Pharmacology & Pharmacy
Medicine, Research & Experimental ; Pharmacology & Pharmacy
|WOS Accession No|
Cited Times [WOS]:0
|Document Type||Journal Article|
|Department||Department of Biomedical Engineering|
1.Department of Biomedical Engineering,Southern University of Science and Technology (SUSTech),Shenzhen,China
2.Shenzhen Institute of Synthetic Biology,Shenzhen Institutes of Advanced Technology (SIAT),Chinese Academy of Sciences,Shenzhen,518055,China
3.Guangzhou Laboratory,Guangzhou,No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangdong Province,510005,China
|First Author Affilication||Department of Biomedical Engineering|
|Corresponding Author Affilication||Department of Biomedical Engineering|
|First Author's First Affilication||Department of Biomedical Engineering|
Liu，Zhao,Zhang，Chen,Cui，Beiming,et al. Targeted EpCAM-binding for the development of potent and effective anticancer proteins[J]. BIOMEDICINE & PHARMACOTHERAPY,2023,161.
Liu，Zhao.,Zhang，Chen.,Cui，Beiming.,Wang，Yijie.,Lim，Kaisheng.,...&Ho，Chun Loong.(2023).Targeted EpCAM-binding for the development of potent and effective anticancer proteins.BIOMEDICINE & PHARMACOTHERAPY,161.
Liu，Zhao,et al."Targeted EpCAM-binding for the development of potent and effective anticancer proteins".BIOMEDICINE & PHARMACOTHERAPY 161(2023).
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