Could beating cancer be as simple as getting a vaccine? That is the premise behind Dr. Zachary Morris’s research.
Morris and his colleagues at the UW Carbone Cancer Center have shown in mouse models of cancer that they can combine radiation therapy and immunotherapies to teach the immune system to specifically recognize and fight that mouse’s cancer.
“Our approach differs from conventional vaccination, in that we’re not giving the mice something specific for its immune system to recognize,” Morris says. “Instead, we’re using locally directed treatments like radiation in one of the mouse’s tumors and then giving the mouse treatments that will stimulate its immune system to recognize these damaged cancer cells. In essence, we’re turning that targeted tumor site into a personalized anti-cancer vaccine.”
Perhaps most exciting about this treatment approach is that it has the potential to not only treat the targeted tumor site but other metastatic tumor sites as well. Also, like standard vaccines, this therapy gives the mice immune memory, such that they fight off a later challenge with the same tumor. The pre-clinical data is so promising that Morris and his collaborators at UW Carbone have submitted a phase I clinical trial to treat metastatic melanoma patients using this approach. They hope to have all the approvals in place to open this trial to patients at UW by the end of 2018.
Still, there are areas that remain a challenge in this new treatment approach, including metastases to the brain.
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.
“The brain is a sort of sanctuary site for many cancers, because many chemotherapy drugs won’t cross the blood-brain barrier,” Morris says. “But the immune system does – activated immune cells have access to the brain.”
With funding from Garding Against Cancer, Morris and his team first showed that the immune memory that develops from their personalized cancer vaccine treatment approach is able to effectively fight and eliminate the same type of cancer cells if they are implanted in the brain several weeks after first treating a tumor in the mouse’s flank. However, if they gave the mice tumors in the flanks and brain at the same time, more closely mimicking a cancer patient with brain metastases, the mouse typically succumbed to the brain metastases.
“The results are promising, because they suggest that we can eradicate sites of disease in the brain once an effective anti-tumor immune response is generated,” Morris says. “Yet, sites of disease in the brain do not respond as well as those in the mouse’s flanks, and we are now doing experiments to look at what’s different about the tumor environment and the immune cells in these locations.”
Morris expects that the observations his group makes about the immune environment in brain metastases may also teach them something about the immune environment in primary brain tumors.
“We suspect that there are major differences in the immune environment for tumors in the brain compared to other locations,” Morris says. “If we can understand what those differences are, we hope to then develop new approaches to make our vaccine strategy and other immunotherapies more effective against tumors in the brain.”
University of Wisconsin