Researchers Identifies that Oncolytic Adenovirus Expresses the HAb18 and Interleukin 24 Genes Exhibits Enhanced Antitumor Activity in Hepatocellular Carcinoma Cells

Hepatocellular carcinoma (HCC) is characterized by alterations in multiple genes. High expression of transmembrane glycoprotein CD147 on the surface of HCC cells promotes proliferation. The monoclonal antibody HAb18 recognizes CD147.

 

A team of scientists led by Prof. LIU Xinyuan at the Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), have constructed an oncolytic adenoviral vector coexpressed HAb18 with interleukin 24 through the use of F2A linker (it was the IL24 armed antibody gene), which will decrease HCC cell viability to a greater degree than either ZD55-HAb18（oncolytic adenoviral vector expressed HAb18） or ZD55-IL24（oncolytic adenoviral vector expressed IL24）alone. ZD55-HAb18-IL24（oncolytic adenoviral vector coexpressed HAb18 with interleukin 24） also induced apoptosis and autophagy in PLC/PRF/5 HCC cells. Intratumoral injection of ZD55-HAb18-IL24 suppressed tumor growth in a PLC/PRF/5 xenograft model. The results suggest that the antitumor cytokine armed antibody gene will elicit a stronger antitumor effect than the antibody alone, and that this strategy could broaden the applications of antibody-based therapies in HCC.

 

This study entitled “An oncolytic adenovirus that expresses the HAb18 and interleukin 24 genes exhibits enhanced antitumor activity in hepatocellular carcinoma cells” was published online by Oncotarget on 9 August, 2016.

 

This work was supported by grants from the Chinese Academy of Sciences and the National Natural Science Fund.

Figure 1: ZD55-HAb18-IL24 repressed tumor growth in a PLC/PRF/5 xenograft model. (Image provided by Prof. LIU Xinyuan’s lab)

 

AUTHOR CONTACT:

Prof. LIU Xinyuan, Principal Investigator, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, P. R. China.

Email: xyliu@sibcb.ac.cn

Phone: +86-21-54921256

 

KEYWORDS: oncolytic adenovirus, HAb18, CD147, interleukin 24, hepatocellular carcinoma

 

NEWS ABSTRACT:

The researchers constructed an oncolytic adenoviral vector to express HAb18 (ZD55-HAb18) in HCC cells. Interleukin 24 (IL24) was co-expressed through the use of an F2A linker. ZD55-HAb18-IL24 decreased HCC cell viability to a greater degree than either ZD55-HAb18 or ZD55-IL24 alone. ZD55-HAb18-IL24 also induced apoptosis and autophagy in PLC/PRF/5 HCC cells. Intratumoral injection of ZD55-HAb18-IL24 repressed tumor growth in a PLC/PRF/5 xenograft model. The results suggest that antibody-antitumor gene conjugation elicited a stronger antitumor effect than the antibody alone, and that this strategy could broaden the applications of antibody-based therapies in HCC.