// So Young Yoo 1, 2 , Seo Young Bang 1 , Su-Nam Jeong 1 , Dae Hwan Kang 2, 3, 4 , Jeong Heo 3, 4 1 BIO-IT Foundry Technology Institute, Pusan National University, Busan 609-735, Republic of Korea 2 Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 626-770, Republic of Korea 3 Department of Internal Medicine, College of Medicine, Pusan National University and Medical Research Institute, Busan 602-739, Republic of Korea 4 Republic of Korea Research Institute, Busan 602-739, Republic of Korea Correspondence to: So Young Yoo, e-mail: yoosy2@gmail.com and yoosy@pusan.ac.kr Jeong Heo, e-mail: sodium@korea.com Keywords: stem cell-like colon cancer cells, oncolytic virus, cancer-favoring vaccinia virus, Wyeth strain, resistance Received: August 15, 2015 Accepted: February 06, 2016 Published: February 24, 2016 ABSTRACT Stem cell-like colon cancer cells (SCCs) pose a major challenge in colon cancer treatment because of their resistance to chemotherapy and radiotherapy. Oncolytic virus-based therapy has shown promising results in uncured cancer patients; however, its effects on SCCs are not well studied yet. Here, we engineered a cancer-favoring oncolytic vaccinia virus (CVV) as a potent biotherapeutic and investigated its therapeutic efficacy in terms of killing SCCs. CVV is an evolved Wyeth strain vaccinia virus (EVV) lacking the viral thymidine kinase. SCC models were established using human or mouse colon cancer spheres, which continuously expressed stemness markers. The cancer-favoring characteristics and different cytotoxic pathways for killing cancer cells successfully overrode general drug resistance, thereby killing colon cancer cells regardless of the presence of SCCs. Subcutaneously injected HT29 spheres showed lower growth in CVV-treated models than in 5-Fu-treated models. Intraperitoneally injected CT26 spheres induced tumor masses in the abdominal region. CVV-treated groups showed higher survival rates and smaller tumor mass formation, compared to 5-Fu-treated groups. Interestingly, the combined treatment of CVV with 5-Fu showed improved survival rates and complete suppression of tumor mass. The CVV developed in this study, thus, effectively suppresses SCCs, which can be synergistically enhanced by simultaneous treatment with the anticancer drug 5-Fu. Our novel CVV is highly advantageous as a next-generation therapeutic for treating colon cancer.
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