Biodesign researchers offer new approach to small-cell lung cancer treatment with oncolytic virotherapy

April 30, 2019

Intensive investigations into the nature of cancer have given rise to innovative and unorthodox approaches to countering this deadly affliction. A recent and exciting avenue of cancer treatment involves targeting malignant cells with specialized viruses that can kill cancer cells while ignoring healthy tissue, a technique known as “oncolytic virotherapy.”

The process involves administering an oncolytic virus, which infects and breaks down cancer cells but does not harm healthy self-cells. This therapy may be administered alone or in conjunction with other common therapies like radiation or chemotherapy drugs. Rahman Masmudur Rahman is an associate research professor for the Biodesign Center for Immunotherapy, Vaccines and Virotherapy. Download Full Image

One particular virus, known as myxoma, has shown significant promise, due to its highly selective nature. When introduced into a tumor, myxoma destroys cancer cells but is harmless to healthy neighboring cells. An oncolytic virus of this type, should its cancer-fighting capacity hold up in clinical trials, offers a silver-bullet for cancer, unlike traditional treatments including radiation and chemotherapy, which often kill both cancer cells and healthy cells indiscriminately.

Myxoma virus is one of the best documented cases of host-virus coevolution. The natural target of the virus is the European rabbit, in which it causes myxomatosis, a lethal disease. In humans, however, the virus is harmless, except when it encounters a cancer cell. A thorough understanding of myxoma’s lethal affinity for cancer is still something of a puzzle and much additional research into the virus’ cancer-terminating nature is needed.

In a recent study published by the Journal of Clinical Investigation, the myxoma virus was used to treat small-cell lung cancer (SCLC) in a genetically engineered mouse (GEM) model. SCLC is characterized by a high incidence in the U.S. and a low five-year survival rate that is not much improved by common therapies, making it the perfect candidate for testing the efficacy of oncolytic virotherapy.

Biodesign researchers Masmudur Rahman, an associate research professor for the Biodesign Center for Immunotherapy, Vaccines and Virotherapy, and Grant McFadden, the center director and a professor in the School of Life Sciences, collaborated with University of Florida to tackle this project.

“I have been studying myxoma virus biology and use of myxoma virus for cancer treatment for more than 12 years,” Rahman said. “When we were at University of Florida, we were looking for genetically engineered mouse cancer models that we can use for testing myxoma virus oncolytic virotherapy. We found that the lab of Zajac-Kaye and Frederic Kaye had developed the lung cancer model described in the paper and then we started collaborating with them.”

Although oncolytic therapy — a hot topic in cancer research — has gained a significant amount of traction, this is the first report of testing a GEM mouse model with SCLC.

“The virus propagated within the lung tumor tissues, but not in normal lung tissues, and induced a localized immune response to the virus-infected tumor beds that cleared the virus within a week of the infection and also caused a prolongation of life.”

The researchers also combined myxoma virus with a standard drug used to treat SCLC in human patients, like cisplatin. This further increased the survival rate and the overall immune response to the tumor.

This study showed that in addition to myxoma virus being capable of inducing immune cell infiltration, it also yields very little toxicity.

“SCLC tumors are immunosuppressive, so based on our observation that myxoma virus not only kills the tumor cells, but also recruits the immune cells in the tumor bed, we think myxoma virus will be a better therapeutic than the current therapies,” Rahman said. “Oncolytic virus mediated therapy has less or no toxicity to the normal cells than the traditional treatments.”

Although researchers were able to reinforce the validity of oncolytic virotherapies in treating cancers alone and with other common drugs, there are more studies to be done.

“Our next step is to test different armed myxoma virus constructs that will further increase the recruitment of immune cells in the tumor bed,” Rahman added. “We also like to test myxoma virus in combination with immune checkpoint inhibitors.”     

These studies are conducted in the hope that these therapies could one day mediate hard-to-treat cancers in humans. Findings such as these could further these efforts.

“A new company called OncoMyx is currently being launched in Phoenix to test next-generation armed myxoma virus constructs in human clinical trials against a variety of human cancers, including lung cancer,” McFadden said.

Gabrielle Hirneise

Assistant science writer , Biodesign Institute


LA high schoolers say HOLA to ASU Downtown Phoenix campus for a glimpse of college life

April 30, 2019

A budding partnership between Watts College of Public Service and Community Solutions and Heart of Los Angeles (HOLA) recently brought a dozen LA sophomores and juniors to the Arizona State University Downtown Phoenix campus for an immersive college experience.

As ASU begins establishing its newest location in downtown Los Angeles at the Herald Examiner building, this growing partnership with HOLA — a vital resource for youth in the area — will serve to strengthen ties with the LA community. HOLA teens throw up their pitchforks for a group photo in front of Wells Fargo Arena HOLA teens pose for a group photo outside Wells Fargo Arena where they watched an ASU basketball game. Photo courtesy of Heart of Los Angeles

HOLA is nonprofit organization currently serving over 2,100 youth ages 6 to 24. It provides underserved youth with free, exceptional programs in academics, arts and athletics within a nurturing environment, empowering them to develop their potential, pursue their education and strengthen their communities.

Watts College hosted HOLA’s Southwest Airlines pre-alumni scholars in downtown Phoenix for an overnight campus stay in February, offering the high school students a taste of college life. The 2019 visit was the first, with the goal of making the visit an annual occurrence.

From Sunday to Monday, HOLA students toured the campus, participated in college classes and college-readiness workshops, watched the ASU Sun Devils beat the California Golden Bears men’s basketball team 69-59 and talked with current Watts College student Xochilt Zelaya.

Zelaya, a senior in the School of Public Affairs, is from the Koreatown neighborhood in Los Angeles close to where HOLA is located, which made it easy for her to connect with the students.

“As an L.A. native who transferred over to ASU, it was exciting to see more people from my community wanting to take the same educational route I did,” Zelaya said.

“HOLA is an incredible organization that is nurturing young people to see themselves as agents of change in their communities, creating pathways to education for their families,” said Jonathan Koppell, dean of Watts College.

“That’s why this partnership is so important to me. Watts College exists to make a difference in communities, and supporting the goals of young people like HOLA’s scholars is core to our mission.”

Along with making the overnight campus visit an annual one, Watts College will sponsor four HOLA students per year (sophomores, juniors or seniors) with scholarships to attend “SummerUP,” an ASU camp held on the West campus, where students are mentored on college readiness and get a taste of university-level, hands-on learning in areas like forensic science, coding, global entrepreneurship and game design.

“Watts College’s consideration shown to our scholars is immensely helpful in our mission to support aspiring college students,” said Anthony Gilmore, scholarship coordinator for HOLA. “Our students have not stopped talking about their adventure in Arizona and have now been exposed to what could be when studying out of state.”

HOLA CEO Tony Brown added, “ASU's track record of sharing its resources with communities striving to reach their full potential is phenomenal, and HOLA is thrilled to be working with them to bring relevant opportunities to our neighborhood.”

The Watts College-HOLA connection exists thanks to Watts College alumnus Alan Adelman, one of HOLA's longest-standing board members and senior equity fund manager and senior equity analyst at Frost Bank.

Lisa Rolland-Keith

Communications Specialist, Watts College of Public Service and Community Solutions