How to develop viruses into anticancer weapons.

Abstract

Viruses have shaped human history through devastating infections. In addition, virus infection may be responsible for up to 15% of cancer deaths [1]. Nevertheless, certain viruses can be our “friends.” At the end of the 18th century, Edward Jenner used cowpox to protect humans against infection with a lethal pathogen, smallpox. Based on the effectiveness of this “vaccination” process, in the 1960s, the World Health Organization mounted a global vaccination campaign that resulted in the eradication of smallpox [2]. In the mid-20th century, the principle of virus attenuation through adaptation to unnatural hosts was extended to cultured cells: cells from different species were used to select viruses with multiple mutations, reducing replication speed and allowing the immune system to control viral infection. Based on such a “live-attenuated” vaccine, global eradication of another viral disease, rinderpest, was recently achieved [3]. Other global vaccination campaigns, including those against polio and measles, are progressing. In addition, subunit vaccines are proving to be effective against virus-induced cancers, preventing hepatitis B virus–induced hepatocellular carcinoma and human papilloma virus–induced cervical cancer [2, 4]. A new frontier is to develop viruses into anticancer weapons. Many cancers remain incurable despite recent advances in radio-, chemo-, and immunotherapy. Based on their preferential replication in tumor cells, viruses from nine families have progressed to clinical trials of oncolysis: DNA viruses include Adenoviridae, Herpesviridae, Parvoviridae, and Poxviridae and RNA viruses Paramyxoviridae, Picornaviridae, Reoviridae, Retroviridae, and Rhabdoviridae [5, 6]. Recently, a genetically modified herpes simplex virus 1–based oncolytic vector, named talimogene laherparepvec (T-VEC), was approved as cancer therapeutic in the United States and Europe [7]. What are the mechanisms supporting cancer therapy with viruses, and how can oncolytic virotherapy be improved?