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 immunotherapy researcher Dr. Stanley Riddell is all too familiar with after more than two decades of attempting to overcome 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 T cells specially engineered to seek and destroy cancer.
“We are entering, I think, a new era where immunotherapy is going to become as established as surgery, radiation and chemotherapy, and I’m hoping that it’s going to be a lot safer for patients and a lot more effective,” Riddell said.
Riddell is a world leader in a type of immunotherapy called CAR T-cell therapy. In this approach, a patient’s T cells are genetically reprogrammed to carry a synthetic receptor called a chimeric antigen receptor, or CAR, that enables the T cells to bind to and destroy target 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.
Years of research in the lab pointed Riddell to the best kinds of T cells to engineer and created sophisticated cancer-targeting CARs. Finally, in 2013, Riddell and colleagues advanced their first CAR T-cell therapy to the clinic. In this trial, T cells of patients with certain advanced blood cancers are engineered with a CAR that allows them to target cells bearing a marker called CD19 that is commonly found on these cancers.
The trial is still ongoing, but preliminary results are promising: For example, 93 percent of the patients with acute lymphoblastic leukemia achieved remission after their T cells were transformed into cancer fighters.
“In my career in science and in medicine, I think these are amongst the most dramatic responses that I have ever seen with any therapy,” Riddell said.
The patients receiving the experimental CAR T-cell therapy through the trial are different from the average leukemia patient — they’ve been through many prior treatments that didn’t work against their cancers, and “they really had very few treatment options at the time they enrolled in our study,” Riddell said.
Using high-tech techniques, Riddell and his colleagues know that the study participants whose cancers disappear after CAR T-cell infusion are in what’s known as a molecular remission, “which is a really, really deep remission, probably remissions that are deeper than anything they’ve ever had with any prior treatment,” the scientist said.
The results so far from this trial are just the beginning, however. Riddell and his team are working on bringing CAR T cells to the clinic that target other types of advanced cancers, including the blood cancer multiple myeloma and solid tumors like breast cancer and lung cancer. The team is also working to overcome common toxic side effects of CAR T-cell approaches, and crafting better CAR technology to reduce patients’ waiting time and increase the cells’ potency against cancer.
“We’re at the starting line,” Riddell said. “But I think we’re at the starting line where we know that we’re in a race that we actually can win.”
Every time he sees patients in the clinic, Riddell goes back to his research with a new sense of urgency.
“The courage of patients is inspiring, and it makes me realize that we don’t have the best [treatments] yet. We have to do better.”
- Updated Dec. 12, 2016
Fred Hutch’s Dr. Stan Riddell and colleagues are making significant strides in this exciting field, and continue to refine ways to use the human immune system to overcome cancer and other diseases.
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