Creating a Lasting Antitumor Immune Response

What biomedical issue did you address in your research and what did your studies find?

My Ph.D. work studied the use of a virus and the body's immune system as a potential anticancer treatment. This approach, called oncolytic virotherapy, leverages the evolutionary mechanisms of viruses to specifically infect cancer cells and then elicit the body's own immune response to eradicate the infected cells. However, generating a tumor-specific immune reaction is complex (tumors, comprised of the body's own proteins, can easily evade the body's immune surveillance), and creating a sustained immune response to cancer is an additional challenge.

My research aimed to understand how oncolytic viruses and the antiviral immune response can be used as therapy and, further, how we might employ them to generate a lasting, protective antitumor response, in the same way many vaccines protect long-term against infectious diseases. I found that a clinically studied inflammatory oncolytic viral vector called vesicular stomatitis virus (VSV) generates an antiviral response so powerful that it can potentially quash an antitumor immune response. While the therapy can reduce tumor growth, once the virus has cleared, no immune effectors remain to target residual cancer, leading to the potential for tumor recurrence.

After identifying this issue, we explored approaches that combined VSV with other immunotherapies to achieve a balance between antiviral and antitumor immune responses. We found that it's possible to overcome the negative impacts of antiviral inflammation if the viral vector also generates proteins specific to the tumor, which shifts the immune response toward cancer. Our findings provide unprecedented information about the negative impact of antiviral inflammation on antitumor immunity and emphasize promising therapeutic strategies that combat a tumor while preserving tumor-specific immune memory.

What aspects of Mayo's culture helped you grow as a scientist and as a thinker?

The collaborative and flexible academic culture of the graduate school made it possible for me to conduct a project at the intersection of virology and immunology. My thesis advisory committee was comprised of experts from both disciplines, and I was able to take courses on tumor immunology and T-cell engineering, which were not requirements for my degree but were invaluable for my research.

One of the most challenging and rewarding aspects of my Ph.D. was presenting my work at national and international conferences, such as the American Society of Gene and Cell Therapy, the American Society of Virology, and the International Oncolytic Virotherapy Conference. I had to tailor the presentation of my work for each audience and be ready to answer questions that applied to each field. The extended discussions I had with researchers provided new insights about my project that ultimately led to its growth and refinement.