Viruses that Cause and Viruses that Cure Cancer
One of the true research gems at UPMC Hillman Cancer Center is our Cancer Virology Program, which is now being led by Dr. Shou-Jiang (S.J.) Gao, who joined Hillman this past April. The investigators who belong to this program are engaged in studying the mechanisms by which tumor viruses cause both solid and hematological malignancies to develop, as well as the ways in which modified viruses can be used to kill tumor cells.Viruses that Cause Cancer
Drs. Yuan Chang and Patrick Moore are the winners of numerous national and international awards for their joint discovery of TWO of the just seven known tumor viruses—Kaposi Sarcoma Herpes Virus (KSHV) in 1994, and Merkel Cell Virus (MCV) in 2008. KSHV is the virus that causes two AIDS-associated malignancies—Kaposi’s sarcoma and primary effusion lymphoma (PEL)—and MCV is the virus that leads to Merkel cell carcinoma—a highly aggressive form of skin cancer. Funded by a National Cancer Institute (NCI) Outstanding Investigator Award (Dr. Moore) and prestigious American Cancer Society Professorships (both Drs. Chang and Moore), they are both members of the National Academy of Sciences, and Dr. Chang was appointed by President Obama as a member of the National Cancer Advisory Board. Currently exploring the mechanistic areas in which virus- and non-virus-caused cancers overlap, Drs. Chang and Moore also continue to apply their own novel methodology toward discovery of any as-of-yet unknown viruses that can lead to human cancer.
Two former trainees from the Chang-Moore lab—Dr. S.J. Gao and Dr. Masahiro Shuda—now lead their own Hillman labs, which respectively focus on KSHV and MCV. Dr. Gao was featured in the April 2018 Director’s Message because of the large number of NCI grants that he brought to Hillman with his recruitment from the University of Southern California.
Dr. Kathy Shair, who is the recipient of an American Cancer Society Research Scholar Grant, and Dr. Nara Lee, study Epstein-Barr Virus (EBV). More often recognized as the causative pathogen of mononucleosis, EBV can also cause naso-pharyngeal carcinoma (a head and neck cancer that is more common in Asia) and Burkitt’s lymphoma (a pediatric cancer that is more common in Africa).Modified Viruses to Treat Cancer
The same features that makes viruses dangerous to normal, healthy cells—the ability to infect, replicate many new copies of itself, and then kill host cells in a repetitive cycle—are being exploited to kill tumor cells. The viruses being engineered to kill cancer cells differ from those that cause illness, in that they are designed to only infect tumor cells and not cause the diseases with which they are usually associated. Dr. Joseph Glorioso is funded by the NCI and Alliance for Cancer Gene Therapy to develop ’oncolytic’ herpes virus particles (virus particles with tumor cell-killing capability) that have been enhanced by the addition of specific non-viral genes, to brain cancer and melanoma in mouse models.
Dr. David Bartlett, from Hillman’s Cancer Immunology Program, is studying how oncolytic viruses can be used to deliver cancer immunotherapy. In a July 2018 publication with his colleagues in the Department of Surgery, he showed that a modified vaccinia virus that codes for a protein that produces anti-tumor immunity, but is inactive for causing smallpox, can reduce colon and ovarian tumor formation in mice. Furthermore, he showed that combining this virus with conventional immunotherapy can dramatically extend survival in a mouse model of advanced colon cancer.
Of tremendous importance in making these and other modified viruses available to patients, Cancer Virology Program member Dr. Andrea Gambotto specializes in manufacturing versions of viruses that are suitable for human use in clinical trials. As you can guess, there are many U.S. Food and Drug Administration requirements to ensure that the generated viral therapies are safe enough to administer.
Speaking of viruses, let’s not forget that this is the time of year to get your flu shot and wash your hands frequently to prevent the spread of flu (influenza virus) and head colds (rhinovirus).
Robert L. Ferris, MD, PhD