In a perfect world, cancer doesn't stand a chance of wreaking havoc. Like a soldier guarding the home shores, the immune system gives marching orders to white blood cells known as T-cells to remain vigilant for an invasion of foreign cells, including cancerous ones. When a T-cell recognizes an invader, it initiates a process that targets that cell for destruction.
But cancer is a formidable foe, one that Stanley Riddell is all too familiar with after more than two decades of waging war against it.
"Tumors are very clever, and they utilize evasion strategies to limit the effectiveness of the immune response," he said.
So he's fortifying the immune system with better weapons: long-living T-cells specially engineered to seek and destroy cancer.
Through adoptive T-cell therapy, Riddell and his fellow researchers extract white blood cells from a cancer patient and expose them to proteins made in abundance by tumor cells. Scientists then identify the few T-cells that recognize the tumor proteins and stimulate those to divide, generating a billions-strong population of cancer-fighting cells that can be infused back into the patient. Ideally, this unique population of T-cells will find its way to the tumor site and annihilate the cancer cells.
"When you see it work, it is so amazing-the bone marrow just goes from being full of leukemia to being in remission, and very large tumors simply melt away," Riddell said.
T-cells, however, have a fatal flaw. They die quickly. And if an immune response isn't sustained, cancer eventually comes back.
Riddell and his colleagues at Fred Hutch knew immunity could last a lifetime-that's how vaccines work. So the researchers reasoned that perhaps they were starting with the wrong T-cells. They began advanced testing on different types of T-cells and found that one type-central memory cells-had the staying power the scientists were seeking. They now had a sustainable starting point for cancer immunotherapy: T-cells with the capacity to survive.
The approach holds promise for fighting different types of leukemia, including chemotherapy-resistant acute lymphoblastic leukemia in children, and breast, ovarian and skin cancers. Riddell's team's insights may also strengthen the work of University of Washington researchers developing potential breast-cancer vaccines.
"We're really trying to move immunotherapy with central memory T-cells into the clinic quickly," Riddell said. "We are excited by the potential for success and believe that this therapy can be applied to several types of cancer."