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.
FINANCIAL DISCLOSURE: This work was supported by the Italian Association for Cancer Research (AIRC), Milan, Italy (projects n. 10353 and 8959); by GR-2008-1135643 grant from the Italian Ministry of Health to L. Menotti, by grants from the Department of Experimental Pathology, University of Bologna (Pallotti funds); by the University of Bologna RFO (Ricerca Fondamentale Orientata); the Italian Ministry for University and Research (PRIN 2008 and 2009 projects); and a grant from Fondazione del Monte di Bologna e Ravenna to G. Campadelli-Fiume. V. Gatta is the recipient of a fellowship from FoRiBiCA Foundation and was also supported through Investigator Grant from AIRC (Associazione Italiana per la Ricerca sul Cancro), Milan, to GCF. V. Grosso is the recipient of a fellowship from FIRC, M. Dall'Ora is the recipient of a PhD fellowship from the University of Bologna. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTERESTS: The authors have declared that no competing interests exist.
PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.plos.org/10.1371/journal.ppat.1003155 (link will go live upon embargo lift)
CITATION: 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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