April 30, 2019

Rapidly advancing cancer immunotherapy

A cancer doctor standing in front of a radiation therapy machine

Madison, Wis. — Though he has only been leading his own research program at the UW Carbone Cancer Center for a few years, Zachary Morris, MD research group’s progress has been moving along at quite a pace.

Around a year ago, Morris, along with Paul Sondel, MD, and others at UW Carbone, had completed a preliminary study in mouse models of metastatic melanoma. They found that giving a combination of radiation and injected immune stimulants to a primary tumor effectively vaccinated the mouse, whose immune system recognized and attacked cancers at most metastatic sites. The findings from these “personalized vaccines” led to development of a clinical trial in metastatic melanoma, expected to open soon at UW Carbone.

Morris’s research was selected for support by Garding Against Cancer funds, and with it he is investigating ways to use the personalized vaccine approach to treat cancers that have generally not responded to immunotherapies in the past, including pediatric cancers. Certain immunotherapy approaches tend to work better on immunologically ‘hot’ cancers, or those cancers with many mutations for the immune system to recognize. Pediatric cancers often fall into the ‘cold’ category, with few mutations. Consequently, many conventional immunotherapy approaches do not work well for these patients.

“But it’s not like we’re throwing out immunotherapy altogether as a potential treatment for pediatric cancers and other immunologically ‘cold’ tumors,” Morris says. “Instead, we’re developing next-generation immunotherapy approaches, which we believe will overcome barriers that have historically limited treatment efficacy for these diseases.”

Morris, Sondel and pediatric oncology fellow Julie Voeller, MD, who is training in Sondel’s lab, are working together to study mouse models of the pediatric cancer neuroblastoma. High-risk forms of the disease have a less than 50% survival rate for affected children.

Garding Against Cancer

Learn how UW Men's basketball coach Greg Gard and his wife Michelle are working with Badgers across the state to advance cancer research in Wisconsin.

“We are now going back to perform additional preclinical studies in mouse models of immunologically ‘cold’ tumors, including neuroblastoma and sarcomas,” Morris says. “By delivering additional immune stimulants into the tumor microenvironment, we are seeking to activate additional types of immune cells to boost the anti-tumor response. We’re beginning to see effects with these additional therapies.”

Morris’s research was also supported by Garding Against Cancer the previous year, where he was looking for ways to improve the personalized vaccine approach for melanoma that had metastasized to the brain.

“Sites of disease in the brain do not respond as well as those in other areas, and we wanted to look at what’s different about the tumor environment and the immune cells in these locations,” Morris noted in a Garding Against Cancer update about his research.

Now, they think they have an idea of what those differences are: the tumor microenvironment surrounding brain metastases appear to harbor excessive numbers of suppressive immune cells. With an idea of why a prior approach is not working, Morris and his team are now working to improve it.

His lab recently found that if low-dose radiation is given to brain tumors at the right time, it appears to kill off the suppressive immune cells – enabling cancer-targeting immune cells to enter and do their job.

“It’s an exciting finding. If low-dose radiation, timed correctly, could overcome this barrier, then that opens the door to a lot of possibilities in both metastases to the brain as well as primary brain cancers like gliomas that arise in the brain,” Morris says. “My lab is just now turning the corner to testing low-dose radiation in primary brain tumors, and primary brain tumors are becoming an active focus of our work.”

Morris is teaming up with UW Carbone brain cancer research scientist Paul Clark, PhD, to continue to apply these findings in cancers in the brain. The team is grateful to philanthropic support from groups like Garding Against Cancer for helping to move their work forward.

“This type of work is exactly at the stage where that money has its effects,” Morris said. “We’re studying these approaches that could work, but we haven’t proven they do work yet. The seed money to do these preliminary studies is so critical because it allows us to test these exciting but unproven approaches that may one day uncover a cure for a previously incurable disease.”