Carcinoembryonic antigen directed herpes viral oncolysis improves selectivity and activity in colorectal cancer

Surgery
Maura ReinblattY Fong

Abstract

G207 is an oncolytic herpes virus whose replicative cycle requires cellular ribonucleotide reductase (RR) for viral DNA synthesis. We attempt to enhance viral cytotoxicity in carcinoembryonic antigen (CEA)-producing colorectal cancer (CRC) cells through CEA-driven RR production. CEA enzyme-linked immunosorbent assay was performed on LS174T and HCT-8 human CRC cells. The CEA enhancer-promoter (CEA E-P) was functionally assessed by luciferase assay. CEA E-P was cloned upstream of UL39, the gene encoding the large subunit of RR. Cells were transfected with CEA E-P/UL39 and infected with G207 for cytotoxicity assays. LS174T, with or without CEA E-P/UL39, were implanted into athymic mouse flanks (n = 28) and treated with G207. CEA levels were 7-fold higher in LS174T versus HCT-8 ( P <.00001). CEA E-P increased luciferase expression 7.5-fold in LS174T ( P <.01), with no increase in HCT-8. G207 cytotoxicity of'CEA E-P/UL39-transfected LS174T cells increased 69% by day 10 versus nontransfected cells ( P <.001), with no significant increase in HCT-8. Combining CEA E-P/UL39 with G207 in LS174T flank tumors resulted in a 65% decrease in tumor volume versus G207, phosphate-buffered saline, or'CEA E-P/UL39 alone ( P <.0001). CEA-driven RR p...Continue Reading

References

Jun 5, 2003·Journal of Cancer Research and Clinical Oncology·Satoshi OkabeKenichi Sugihara

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Citations

Sep 23, 2010·Virology Journal·Katja Sliva, Barbara S Schnierle
Dec 14, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Zhenkun YuRichard J Wong
May 25, 2010·Seminars in Oncology·Susanne G CarpenterYuman Fong
Dec 15, 2015·The Cochrane Database of Systematic Reviews·Brian D NicholsonDavid Mant
Feb 21, 2006·World Journal of Gastroenterology : WJG·Andreas P Sutter, Henry Fechner

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