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Engineered oncolytic herpes virus inhibits ovarian and breast cancer metastases

Date:
February 1, 2013
Source:
Public Library of Science
Summary:
A genetically reprogrammed Herpes simplex virus (HSV) can cure metastatic diffusion of human cancer cells in the abdomen of laboratory mice, according to a new study.

Therapy with R-LM249 of Rag2−/−;Il2rg−/− mice bearing i.p. human SK-OV-3 ovarian carcinoma. (A–C) incidence of peritoneal carcinomatosis, weight of metastatic lesions (mean + SEM) and incidence of ascites fluid in groups of 5–7 mice. Statistically significant differences: panel B, p = 0.007 at Student's t test; panel C, p = 0.027 at Fisher's exact test. (D) control mouse, treated with vehicle (PBS) alone, showing multiple i.p. masses (green arrows); (E) tumor-free mouse treated with R-LM249; (F) distribution of R-LM249 in a mouse bearing multiple i.p. tumors shows that the virus selectively populates and replicates in the HER-2+ masses (green fluorescence: virally-encoded EGFP; yellow-brown florescence: autofluorescence of mouse fur and visceral organs).
Credit: Nanni et al. Preclinical Therapy of Disseminated HER-2 Ovarian and Breast Carcinomas with a HER-2-Retargeted Oncolytic Herpesvirus. PLoS Pathogens, 2013; 9 (1): e1003155 DOI: 10.1371/journal.ppat.1003155

A genetically reprogrammed Herpes simplex virus (HSV) can cure metastatic diffusion of human cancer cells in the abdomen of laboratory mice, according to a new study published January 31 in the Open Access journal PLOS Pathogens. The paper reports on the collaborative research from scientists at the at the University of Bologna and specifically describes that the HSV converted into a therapeutic anticancer agent attacks breast and ovarian cancer metastases.

Past decades have witnessed significant progress in the ability to treat numerous cancers by means of surgery, chemo- and radio-therapy, or combinations thereof. However, many treatments prolong life for a short time only, or are associated with a poor quality of life.

Lead investigator Gabriella Campadelli-Fiume and colleagues re-engineered the entry apparatus of a candidate oncolytic herpesvirus. The reprogrammed virus no longer infects the cells usually targeted by the wild-type virus, nor does it cause herpes-related pathologies. Rather, it acts as a specific weapon against tumor cells that express the HER-2 oncogene.

"Numerous laboratories worldwide are using viruses as more specific weapons against cancer cells, called oncolytic viruses," says Campadelli-Fiume, Professor of Microbiology and Virology. "Safety concerns prevailed so far, and all oncolytic herpesviruses now in clinical trials are debilitated viruses, effective only against a fraction of tumors. We were the first to obtain a herpes virus reprogrammed to enter HER-2-positive tumor cells, unable to infect any other cell, yet preserves the full-blown killing capacity of the wild-type HSV."

Additionally, the laboratory of Pier-Luigi Lollini, Patrizia Nanni and Carla De Giovanni in collaboration with researchers at the Rizzoli Institute, established the new model of human cancer metastases in mice that was used to demonstrate the therapeutic efficacy of the reprogrammed virus.

The positive results obtained in the treatment of experimental metastasis hold the promise that the newly retargeted oncolytic HSV described in PLOS Pathogens is a good candidate to become a novel type of cancer treatment, and represents a key step forward in the path to clinical trials for late stage human breast and ovarian cancers.


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The above story is based on materials provided by Public Library of Science. Note: Materials may be edited for content and length.


Journal Reference:

  1. Patrizia Nanni, Valentina Gatta, Laura Menotti, Carla De Giovanni, Marianna Ianzano, Arianna Palladini, Valentina Grosso, Massimiliano Dall'Ora, Stefania Croci, Giordano Nicoletti, Lorena Landuzzi, Manuela Iezzi, Gabriella Campadelli-Fiume, Pier-Luigi Lollini. Preclinical Therapy of Disseminated HER-2 Ovarian and Breast Carcinomas with a HER-2-Retargeted Oncolytic Herpesvirus. PLoS Pathogens, 2013; 9 (1): e1003155 DOI: 10.1371/journal.ppat.1003155

Cite This Page:

Public Library of Science. "Engineered oncolytic herpes virus inhibits ovarian and breast cancer metastases." ScienceDaily. ScienceDaily, 1 February 2013. <www.sciencedaily.com/releases/2013/02/130201090820.htm>.
Public Library of Science. (2013, February 1). Engineered oncolytic herpes virus inhibits ovarian and breast cancer metastases. ScienceDaily. Retrieved September 21, 2014 from www.sciencedaily.com/releases/2013/02/130201090820.htm
Public Library of Science. "Engineered oncolytic herpes virus inhibits ovarian and breast cancer metastases." ScienceDaily. www.sciencedaily.com/releases/2013/02/130201090820.htm (accessed September 21, 2014).

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