Related Experiment Videos
Oncolytic reovirus against ovarian and colon cancer
Kensuke Hirasawa1, Sandra G Nishikawa, Kara L Norman
1Cancer Biology Research Group and Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, T2N 4N1 Canada.
Abstract:
Reovirus selectively replicates in and destroys cancer cells with an activated Ras signaling pathway. In this study, we evaluated the feasibility of using reovirus (serotype 3, strain Dearing) as an antihuman colon and ovarian cancer agent. In in vitro studies, reovirus infection in human colon and ovarian cell lines was assessed by cytopathic effect as detected by light microscopy, [(35)S]Methionine labeling of infected cells for viral protein synthesis and progeny virus production by plaque assay. We observed that reovirus efficiently infected all five human colon cancer cell lines (Caco-2, DLD-1, HCT-116, HT-29, and SW48) and four human ovarian cancer cell lines (MDAH2774, PA-1, SKOV3, and SW626) which were tested, but not a normal colon cell line (CCD-18Co) or a normal ovarian cell line (NOV-31). We also observed that the Ras activity in the human colon and ovarian cancer cell lines was elevated compared with that in normal colon and ovarian cell lines. In animal models, intraneoplastic as well as i.v. inoculation of reovirus resulted in significant regression of established s.c. human colon and ovarian tumors implanted at the hind flank. Histological studies revealed that reovirus infection in vivo was restricted to tumor cells, whereas the surrounding normal tissue remained uninfected. Additionally, in an i.p. human ovarian cancer xenograft model, inhibition of ascites tumor formation and the survival of animals treated with live reovirus was significantly greater than of control mice treated with UV-inactivated reovirus. Reovirus infection in ex vivo primary human ovarian tumor surgical samples was also confirmed, further demonstrating the potential of reovirus therapy. These results suggest that reovirus holds promise as a novel agent for human colon and ovarian cancer therapy.
Insights
Reovirus effectively targets and eliminates human colon and ovarian cancer cells, sparing normal tissues. This oncolytic virus shows significant tumor regression in preclinical models, indicating its therapeutic potential.
Area of Science:
- Oncology
- Virology
- Cancer Biology
Background:
- Reovirus selectively targets cancer cells with activated Ras signaling.
- Oncolytic viruses are a promising cancer therapy approach.
Purpose of the Study:
- To evaluate reovirus (serotype 3, strain Dearing) as a potential treatment for human colon and ovarian cancers.
- To assess reovirus efficacy in vitro and in vivo.
Main Methods:
- In vitro: Assessed reovirus infection via cytopathic effect, viral protein synthesis, and progeny virus production in human cancer and normal cell lines.
- In vivo: Utilized animal models with human colon and ovarian tumors, employing intraneoplastic and intravenous inoculation.
- Ex vivo: Confirmed reovirus infection in primary human ovarian tumor samples.
Main Results:
- Reovirus efficiently infected and replicated in human colon and ovarian cancer cell lines, but not normal cells.
- Elevated Ras activity was observed in cancer cell lines compared to normal cells.
- Significant tumor regression and inhibition of ascites formation were observed in animal models.
- Reovirus infection was confined to tumor cells in vivo, sparing normal tissues.
Conclusions:
- Reovirus demonstrates selective oncolytic activity against human colon and ovarian cancer cells.
- Preclinical data support reovirus as a promising novel therapeutic agent for these cancers.
- Further clinical investigation of reovirus therapy is warranted.