Research Papers:

Efficacy of CD46-targeting chimeric Ad5/35 adenoviral gene therapy for colorectal cancers

Young-Suk Cho, Manh-Hung Do, Se-Young Kwon, Changjong Moon, Kwonseop Kim, Keesook Lee, Sang-Jin Lee, Silvio Hemmi, Young-Eun Joo, Min Soo Kim _ and Chaeyong Jung

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Oncotarget. 2016; 7:38210-38223. https://doi.org/10.18632/oncotarget.9427

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Young-Suk Cho1,*, Manh-Hung Do1,*, Se-Young Kwon1, Changjong Moon2, Kwonseop Kim3, Keesook Lee4, Sang-Jin Lee5, Silvio Hemmi6, Young-Eun Joo7, Min Soo Kim8, Chaeyong Jung1

1Department of Anatomy, Chonnam National University Medical School, Gwangju, Korea

2College of Veterinary Medicine, Chonnam National University, Gwangju, Korea

3College of Pharmacy, Chonnam National University, Gwangju, Korea

4Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Korea

5Genitourinary Cancer Branch, Research Institute of National Cancer Center, Goyang, Gyeonggi-do, Korea

6Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland

7Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea

8Department of Statistics, College of Natural Sciences, Chonnam National University, Gwangju, Korea

*These authors have contributed equally to this work

Correspondence to:

Min Soo Kim, e-mail: [email protected]

Chaeyong Jung, e-mail: [email protected]

Keywords: CD46, adenovirus, gene therapy, colorectal cancer

Received: February 01, 2016     Accepted: April 28, 2016     Published: May 18, 2016


CD46 is a complement inhibitor membrane cofactor which also acts as a receptor for various microbes, including species B adenoviruses (Ads). While most Ad gene therapy vectors are derived from species C and infect cells through coxsackie-adenovirus receptor (CAR), CAR expression is downregulated in many cancer cells, resulting inefficient Ad-based therapeutics. Despite a limited knowledge on the expression status of many cancer cells, an increasing number of cancer gene therapy studies include fiber-modified Ad vectors redirected to the more ubiquitously expressed CD46. Since our finding from tumor microarray indicate that CD46 was overexpressed in cancers of the prostate and colon, fiber chimeric Ad5/35 vectors that have infection tropism for CD46 were employed to demonstrate its efficacy in colorectal cancers (CRC). CD46-overexpressed cells showed a significantly higher response to Ad5/35-GFP and to Ad5/35-tk/GCV. While CRC cells express variable levels of CD46, CD46 expression was positively correlated with Ad5/35-mediated GFP fluorescence and accordingly its cell killing. Injection of Ad5/35-tk/GCV caused much greater tumor-suppression in mice bearing CD46-overexpressed cancer xenograft compared to mock group. Analysis of CRC samples revealed that patients with positive CD46 expression had a higher survival rate (p=0.031), carried tumors that were well-differentiated, but less invasive and metastatic, and with a low T stage (all p<0.05). Taken together, our study demonstrated that species B-based adenoviral gene therapy is a suitable approach for generally CD46-overexpressed CRC but would require careful consideration preceding CD46 analysis and categorizing CRC patients.

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