Scientists at the University of Wisconsin’s School of Medicine and Public Health are exploring new ways to make cancer cells more susceptible to attack by the body’s immune system.
Working in mice, a team led by Jamey Weichert, professor of radiology, and Zachary Morris, professor of human oncology, combine two different techniques in their approach, using targeted radionuclide therapy, which provides a low dose of radiation d cell weakening specifically for cancer cells, followed by immunotherapy, which helps the immune system recognize and destroy cancer cells. Animal research lays the foundation for future clinical trials in humans and veterinarians.
“This has a great advantage because we can target tumors systemically, regardless of their number and anatomical location,” Weichert explains. “I often describe this as destroying the tumor with this small amount of radiation to aid recognition of the immune system.”
The team received $ 12.5 million in funding from the National Cancer Institute to further develop this approach to treat a variety of cancers, including prostate and canine cancers.
The research effort includes four projects and four research and support centers led by Weichert, Morris and a group of other UW researchers – Madison – many of whom are members of the University of Wisconsin Carbon Cancer Center.
Unlike traditional external beam radiation therapy, which is given to all or a large part of the body in an undirected manner, therapy with targeted radionuclides involves the attachment of a radioactive atom (also called a radionuclide) to a molecule that is primarily taken up by tumor cells.
Weichert’s team uses a radioactive element and a molecule that mimics a type of lipid found in rapidly dividing cancer cells. They also use imaging techniques to allow precise dosing of the agents, which are injected into the bloodstream.
Scientists have found in mice that using immunotherapy in combination with targeted radionuclide therapy is more powerful than any approach alone. They will study other combinations of different immunotherapy agents to fight the many ways cancer can escape the immune system.
For example, some cancer cells have a way of “shutting down” immune cells that try to attack them. The team uses immune checkpoint inhibitors, which are drugs that block the ability of cancer cells to neutralize immune cells, so immune cells have a chance to fight.
Another area of research focuses on how the immune cells themselves are activated. Paul Sondel, professor of pediatrics and human oncology, is studying an “in situ vaccine” that attracts immune cells to the tumor and activates them to recognize and kill cancer cells at the tumor site. The technique trains the immune system to retain memory for a specific cancer much like vaccines against infectious diseases, which instruct the immune system to recognize pathogens, such as bacteria and viruses.
Douglas McNeel, professor of medicine, applies this synergistic approach to prostate cancer, combining his team’s work on prostate tumor vaccines with targeted radionuclide therapy. His team will examine whether targeted radiation therapy will weaken the tumor first, resulting in better performance of the immune-stimulated cell vaccine that attacks prostate cancer cells.
Morris likens these combined therapies to a bulldozer destroying a tumor.
The bulldozer ignition needs to be turned on, and in some cases a cancer vaccine can aid this process. Starting and accelerating the excavator requires fuel, which can be supplied by drugs that grow and proliferate anti-cancer immune cells. Checkpoint inhibitors can further accelerate acceleration by disabling the brakes of the immune system. And when there are multiple tumors, targeted radionuclide therapy can spread through the bloodstream to any tumor in the body. This opens the way for the anti-tumor immune response to kill cancer cells all over the body.
The group has so far studied a limited set of radionuclide therapies and targeted immunotherapies – preliminary work made possible by a UW2020 grant from UW – Madison Office of the Vice Chancellor for Research and Graduate Education and the Wisconsin Alumni Research Foundation. Funding from the National Cancer Institute will allow them to expand their work to include different types of these therapies and to study them alone and in combination.
“The number of variables here is starting to get huge and shows that we know very little about how to optimize the interactions between these therapies,” Morris said. “The only way to really understand this is to experimentally make head-to-head comparisons in a very controlled fashion, because this concession gives us the means to do that.”
Other people involved in this group are specialists in data analysis, radiation dosing, the production of therapeutic agents and the application of these treatments in canine cancer patients, when the owners consent to them. try for experimental treatment. They include Kyungmann Kim, Michael Newton, Bryan Bednarz, Joe Grudzinski, Reinier Hernandez, Jonathan Engle and David Vail.
“There’s really only one or two other institutions in the country that can do this kind of research, that have access to the expertise and the resources that are needed,” Weichert says. “We have the best people in the world in each of these disciplines. We believe we are launching a new area of cancer therapy here. It’s very exciting and the research team is amazing.