Use of Replicating Oncolytic Adenoviruses in Combination Therapy for Cancer

Abstract

ABSTRACT

Expression of the coxsackievirus- and adenovirus receptor in gastrointestinal cancer correlates with tumor differentiation

“…Therapeutic adenoviruses represent a new therapeutic modality that can be designed to specifically replicate in and kill cancer cells. Clinical studies demonstrate that such viruses can safely be administered locally, regionally and systemically 2 and that these agents have efficacy in gastrointestinal cancer, in particular when administered by intrahepatic arterial infusion. 3 However, objective tumor responses were observed in only a small number of the patients.…”

Oncolytic adenovirus armed with human papillomavirus E2 gene in combination with radiation demonstrates synergistic enhancements of antitumor efficacy

“…Changes caused by radiation both at the cell surface and in the cytoplasm and nucleus may all contribute to improved virus uptake by tumor cells. 37 The synergistic cytotoxicity was also observed in the in vivo SiHa xenograft model: combination of 1 Â 10 8 PFU M5 with RT significantly inhibited the tumor growth and increased the survival probability compared to either agent alone. Moreover, in the combination group, no significant body weight loss was observed.…”

“…The mode of action of radiation, chemotherapy and virotherapeutic agents is different and would not be expected to lead to the development of cross-resistance. 21 Thus, combination treatment has great potential for translation into effective clinic therapy in the immediate future. In this study, the combination of M5 and radiation resulted in a synergistic increase in cell killing activity in vitro compared to that resulting from treatment with either agent alone.…”

“…20 Such Ads vectors have entered clinical trials where their advantages including combination with radiotherapy or chemotherapy to increase therapeutic efficacy and potentially decrease toxic side effects have been demonstrated. 21 In this study, we constructed and characterized a novel E1A CR2-deleted Adv5, named M5, with the whole open reading frame (ORF) of HPV16 E2 gene inserted into the deleted 6.7K/gp19K region to establish a selectively replicative Adv-mediated gene therapy strategy for CC. Careful assessment was made for specific targeting of tumor cells by HPV E2 gene and the synergistic efficacy of combined treatment with M5 and radiation treatment.…”

Indole-3-carbinol (I3C) increases apoptosis, represses growth of cancer cells, and enhances adenovirus-mediated oncolysis

“…Combinational therapies have shown enhanced therapeutic effects in vitro and in vivo compared with monotherapy. 37,38 There have been no prior reports of the benefit of dietary supplements to oncolytic virotherapy. In the current study, we discovered synergistic effects of combination of I3C with oncolytic Ads.…”