STM Article Repository

Chan, Kin Tak and Tung, Lai Nar and Lam, Ho Yu and Choi, Mei Yuk and Wong, Mung Yee and Fatima, Sarwat and Tam, Pui Ying and Wang, Hector K. and Liu, Edgar S. L. and Bian, Zhao Xiang and Lee, Nikki P. (2016) Survival Benefit of a Monoclonal Antibody against Cadherin-17 in an Orthotopic Liver Tumor Xenograft Model. Journal of Applied Life Sciences International, 4 (3). pp. 1-10. ISSN 23941103

[thumbnail of Lee432015JALSI22188.pdf] Text
Lee432015JALSI22188.pdf - Published Version

Download (332kB)

Abstract

Aims: Monoclonal antibodies against tumor-related molecules are therapeutic agents for cancers. Promising results support the use of monoclonal antibodies in several cancers such as lung and breast cancer. However, using monoclonal antibodies as therapeutic agents to treat hepatocellular carcinoma (HCC), a major type of liver cancer, is still at the beginning. We have previously generated a monoclonal antibody against cadherin-17 (CDH17), named Lic5. This antibody has proven anti-tumor and cisplatin-sensitizing effect in HCC using a subcutaneous tumor xenograft mouse model.

Study Design and Methodology: To further consolidate our previous finding, we tested the effect of Lic5 alone or in combination with cisplatin or epirubicin on tumor growth inhibition and animal survival using a more advanced orthotopic tumor xenograft model.

Results: Single Lic5, cisplatin and epirubicin treatment inhibited growth of cultured HCC cells using cell proliferation assay, while more significant reductions were observed when cisplatin or epirubicin was used together with Lic5. Similar trends of growth inhibition were observed when the same experimental grouping was applied to treat orthotopic tumor-bearing nude mice. Treatment of Lic5 enhanced survivals of orthotopic tumor-bearing nude mice when compared to the control group. Among all experimental groups, combined Lic5 and epirubicin group yielded the best survival. For next phase antibody humanization, we also identified the complementarity determining regions (CDRs) on variable regions on the light and heavy chain of Lic5.

Conclusion: Together, we have validated the preclinical use of Lic5 in an orthotopic HCC xenograft model. Our successful identification of CDRs constitutes the first step in synthesizing humanized Lic5.

Item Type: Article
Subjects: GO for ARCHIVE > Biological Science
Depositing User: Unnamed user with email support@goforarchive.com
Date Deposited: 04 Jul 2023 04:57
Last Modified: 22 Jan 2024 04:47
URI: http://eprints.go4mailburst.com/id/eprint/879

Actions (login required)

View Item
View Item