New viruses for cancer therapy: the measles paradigm

New viruses for cancer therapy: the measles paradigm Prof. Roberto Cattaneo Professor of Biochemistry/Molecular Biology, Mayo Clinic College of Medicine

  • Date: 02 December 2016

  • Event location: Aula Ex Esercitazioni, Via San Giacomo 12, Bologna

Contact Name: Commissione Ricerca e Attività Correlate

Attendees: Biosketch, Roberto Cattaneo received his undergraduate degree from the University of Geneva, Switzerland, and his PhD from the University of Heidelberg, Germany, where he established the transcription map of hepatitis B virus. During his postdoctoral training on measles virus persistent infections at the University of Zurich, Switzerland, he discovered adenosine-to-inosine hypermutation of viral RNA, and messenger RNA editing by polymerase stuttering. In 1991 Dr. Cattaneo received the Swiss Talents for Academic Research and Teaching award. The goal of Dr. Cattaneo group is to understand virus biology, tropism, and to make viruses into vectors that can deliver genes and treat disease, in particular different types of cancer. After moving to the Department of Molecular Medicine of the Mayo Clinic in 1999, he established the Virology and Gene Therapy track of Mayo Graduate School. Basic research highlights include the characterization of how measles virus interacts with its receptors and fuses cell membranes, and the discovery of a receptor mediating virus emergence at an anatomic location facilitating aerosol formation. This “exit receptor” explains why measles is the most contagious human virus. Prof. Cattaneo has authored more than 140 primary publications, many reviews, and several patents. He serves on the editorial board of several journals, and has held leadership positions in the American Society for Gene and Cell Therapy and the American Society for Virology. His honors include state-of-the-art lectures at national and international congresses of Microbiology, Virology, and Gene Therapy. Several of his students and postdoctoral fellows are full professors at Universities in Europe and North America

Abstract

The concept of virotherapy originates from clinical reports of cancer regression coincident with natural viral infections. Viruses replicate preferentially in cancer cells because mutations that favor uncontrolled cell growth often disable innate immune defenses. To reach tumors, several oncolytic take advantage of junctional proteins as receptors to break epithelial barriers (Mateo et al. 2015 J Cell Sci., 128, 451-459). While initially virotherapy was based on natural viruses, current clinical trials are based on viruses genetically modified for the selective elimination of cancer. These trials have reported that all the tested viruses (Adenoviridae, Herpesviridae, Paramyxoviridae, Parvoviridae, Picornaviridae, Poxviridae, Reoviridae, Retroviridae and Rhabdoviridae) are safe. The most promising new viruses are now in advanced efficacy trials. We focus here mainly on cancer therapy based on an enveloped RNA virus with a helical nucleocapsid, measles virus (Pfaller et al., 2015, Virology 479-480C, 331-344). We discuss how its cell-associated replication process facilitates the development of new cancer vectors that are targeted at the cell entry and post-entry levels, armed for enhanced efficacy, and shielded to avoid neutralization. Live imaging at different times after treatment is used pre-clinically and clinically to identify the sites of viral replication, and document the mechanisms of oncolysis. A current key challenge is to develop viruses that achieve therapeutic synergy with available cancer treatments (Miest and Cattaneo, 2014, Nature Rev. Microbiol. 12, 23-34).