Haydn Kissick, PhD (right) with lab manager Petra Gregorova.
The Cancer Research Institute has awarded a five-year STAR program grant of $1.25 million to Haydn T. Kissick, PhD, assistant professor in the Department of Urology at the Emory School of Medicine and cancer immunology researcher at Emory’s Winship Cancer Institute, to search for answers to the difficult question of how T cells can help protect the body against cancer. The prestigious STAR (Scientists TAking Risks) award gives mid-career scientists the freedom and flexibility to pursue high-risk, high-reward projects not tied to a specific research agenda, with the potential to make fundamental discoveries in cancer immunotherapy.
Immunotherapy has generated great excitement recently: the idea that cancer could be fought, not through external and invasive processes such as chemotherapy, but by using the body’s own immune system to attack the tumor. However, the road to developing actual therapies has been slow and full of obstacles.
“We know what the immune system's capable of,” Kissick says. “Complete clearance of your cancer in three months is the best situation, and then you never see it again and you're protected from it coming back. If we can pull that off for everyone, this could be the path for many more patients benefitting from immunotherapy.”
The challenge has been to find ways to control the immune system so it attacks only cancer cells rather than healthy cells. Kissick’s research has focused on T cells, a type of white blood cell that originates in bone marrow. When T cells infiltrate into a tumor, it increases chances of survival and response to therapy in almost every type of cancer, but different patients have different levels of T cells, even in a single tumor type, from almost none to more than 20 percent. In particular, the Kissick lab is studying a cytotoxic subset called CD8 T cells, searching for the genetic signaling mechanism that could cause them to target only cancer cells.
“A T-cell is unable to just find a cancer cell and kill it,” Kissick explains. “It has to get very specific instructions from other immune cells so that it can do the right thing. If the signals that tell that stem cell to do the right thing and kill the cancer aren't correct, the immune response breaks down. So it's an orchestration of many cells working together.”
Kissick’s research will use a two-pronged strategy. One project will systematically knock out hundreds of different genes in mice, one by one, using the process of elimination to see which ones tell the CD8 stem cell to become a cancer killer. The second project will administer a drug to prostate cancer patients at Emory Healthcare designed to activate all the immune cells in their tumor at once. They’ll then analyze samples of those tumors in the lab to see if the same gene is present in the human tissue.
A separate but parallel project will look at the relationship between CD8 T cells and a different subset, CD4 T cells, the so-called “helper cells” which can turn on the CD8 cells so they target cancers. Kissick hopes this might be an alternative path to control immune response. “The CD4 T cells are higher up in the food chain,” he says. “They send signals down. We’ll use the CD4 T cell to instruct the CD8 T cell what to do. A good place for us to make drugs to intervene in those communications, that can tell the immune system to kill the cancer better.”
The Cancer Research Institute, founded in 1953, is a New York City-based nonprofit that supports research worldwide aimed at harnessing the power of the immune system to develop therapies targeting all forms of cancer. Rather than funding specific research protocols, the Lloyd J. Old STAR Program, named for CRI’s founding scientific director, makes grants for broad research goals based on the promise and quality of recipients’ past work.
Because awardees are expected to be future leaders in cancer immunotherapy, the grant lets recipients follow their own vision along new pathways, even risking failure, to pursue unanticipated, outside-the-box breakthroughs.
Kissick says this broad scope lets him work on related but not perfectly coordinated projects in a way that wouldn’t be possible with conventional funding.
“This grant lets me say, I know the stem cell is very important. I know it's the key for us to make a good immune response to cancer. I'm allowed to say, ‘I don't really know what the signals are, but I think it's really important we work out what those signals are.’ But it is high risk because we're going to search for many things. We're going to be wrong very often. But if we work it out, then I think we've found something that's key to the immune response to almost every cancer.”