Engineered oncolytic herpes virus inhibits ovarian and breast cancer metastases

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 reprogrammed to enter HER-2-positive , 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 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.

More information: Nanni P, Gatta V, Menotti L, De Giovanni C, Ianzano M, et al. (2013) Preclinical Therapy of Disseminated HER-2+ Ovarian and Breast Carcinomas with a HER-2-Retargeted Oncolytic Herpesvirus. PLoS Pathog 9(1): e1003155. doi:10.1371/journal.ppat.1003155

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