Carcinoembryonic antigen directed herpes viral oncolysis improves selectivity and activity in colorectal cancer Journal Article
| Authors: | Reinblatt, M.; Pin, R. H.; Fong, Y. |
| Article Title: | Carcinoembryonic antigen directed herpes viral oncolysis improves selectivity and activity in colorectal cancer |
| 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 production by CEA-secreting CRC cells significantly improves oncolytic viral cytotoxicity and specificity in vitro, and reduces tumor burden in vivo. |
| Keywords: | controlled study; human cell; promoter region; disease course; nonhuman; colorectal cancer; cell death; tumor volume; carcinoembryonic antigen; cell line, tumor; cell assay; enzyme linked immunosorbent assay; colorectal neoplasms; molecular cloning; gene expression regulation, neoplastic; cancer cell; gene therapy; herpes virus; simplexvirus; virus infection; virus replication; genetic code; enzyme assay; disease activity; ribonucleotide reductase; virus virulence; viruses; cytotoxicity test; humans; human; priority journal; article; ribonucleotide reductases |
| Journal Title: | Surgery |
| Volume: | 136 |
| Issue: | 3 |
| ISSN: | 0039-6060 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2004-09-01 |
| Start Page: | 579 |
| End Page: | 584 |
| Language: | English |
| DOI: | 10.1016/j.surg.2004.05.033 |
| PROVIDER: | scopus |
| PUBMED: | 15349105 |
| DOI/URL: | |
| Notes: | Surgery -- Cited By (since 1996):9 -- Export Date: 16 June 2014 -- CODEN: SURGA -- Source: Scopus |
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