Vaccine designed to fight HIV may also fight cancer

A cytomegalovirus (CMV) vaccine platform developed by Oregon Health & Science University (OHSU) is showing promise as a “shield” against cancer. The study was recently published in Science Advances.

Cytomegalovirus, or CMV, is a common virus that infects most people during their lifetime and usually causes mild or no symptoms.

Cancer cells, like many viruses, often evade the immune system by eluding the control of T cells, which help protect the body from infections. OHSU researchers used CMV to transport antigens associated with cancer, which triggered an immune response. This stimulated the production of T cells, which specifically target cancer cells and create long-lasting immune system protection.

"We have shown that cytomegalovirus can induce the production of unusual T cells to cancer antigens, and that these unusual T cells can recognize cancer cells," said Klaus Früh, Ph.D., professor at the Vaccine and Gene Therapy Institute (VGTI) O.H.S.U. "The idea is that by targeting a specific type of T cell against a cancer that the cancer has not encountered before, it will have more difficulty evading immune defenses."

Frew and colleagues Louis Picker, MD, professor at VGTI, and Scott Hansen, PhD, assistant professor at VGTI, have been working on developing this vaccine platform since the early 2000s. In 2016, their startup company OHSU TomegaVax was acquired by San Francisco-based Vir Biotechnology. The company is currently testing the platform as part of a human clinical trial of an HIV vaccine.

Their research initially focused on using the platform as a vaccine against HIV T cells. Although early human clinical trials established the safety of the platform, researchers have since modified the vaccine to produce the desired immune responses. They expect the first data on immune responses from a clinical trial later this year.

Platform expansion

The new study expands their preclinical research, showing the promise of the CMV vaccine platform against cancer.

Researchers used genetically modified Rh-CMV to induce cancer-specific T cells in Rhesus macaques at the OHSU Oregon National Primate Research Center. In their previous preclinical studies, they showed that Rh-CMV could be genetically programmed to stimulate T cells differently than conventional vaccines. These T cells recognize infected cells in a unique way.

They sought to answer two questions: Can a Rh-CMV vaccine induce unusual immune responses to common cancer antigens? And if so, can these unique immune cells recognize and attack cancer cells?

The answer to both questions is yes. The T cell response to cancer antigens was similar to their response to viral antigens in both strength and precision. Working with Mount Sinai Hospital in New York, they also found that when an animal model was exposed to prostate cancer antigen, T cells were activated by prostate cancer cells. This suggests that cancer cells may be targeted by this unique immune response.

"Targeting T cells to cancer antigens isn't easy because you're trying to trigger an immune response to a self-antigen, something the immune system is trained not to respond to," Frew said. "Overcoming this immunological tolerance is a challenge for all cancer vaccines."

Klaus Frueh, Ph.D., a professor at the OHSU Vaccine and Gene Therapy Institute, is researching the potential of cytomegalovirus vaccines. Along with colleagues Louis Picker, MD, and Scott Hansen, PhD, both of VGTI, they found that their vaccine platform shows promise as a "shield" against cancer.

Hope: a cancer vaccine

Frew says there is excitement about the vaccine platform's potential in the fight against cancer. Because T cells induced by CMV vaccines persist for life, this may be especially useful in preventing recurrences of cancers such as prostate or breast cancer. The hope is that if someone has already had prostate cancer, the vaccine will prevent it from coming back.

"If you've had cancer, you spend the rest of your life worrying that it might come back," he said. "So to have a vaccine that can induce cancer-specific T cells that act as an immune shield that continuously patrols your body and protects you for life is just incredible."

Researchers must first determine whether the results obtained in the animal model can be replicated in humans. CMVs are species specific, so Rh CMV may not produce the same immune response in humans. Ongoing clinical trials for HIV will provide early evidence to decide whether further testing and development is worth pursuing. Human clinical trials for other pathogens and cancers are on the horizon.