Last resort cancer therapy holds disease back for more than a decade


CAR-T cell therapy alters T cells — shown here attacking a brain cancer cell — to recognize specific proteins.Credit: Steve Gschmeissner/Scientific photo library

Weeks after receiving an experimental cancer therapy that turns immune cells into tumor hunters, Doug Olson’s doctor sat him down to update him on his progress. “He said, ‘Doug, we can’t find a single cancerous cell in your body,'” Olson recalled. “I was pretty convinced I was done with cancer.”

Olson’s doctors, however, weren’t so sure. It was 2010 and Olson was one of the first people with chronic lymphocytic leukemia to receive the treatment, called CAR-T cell therapy. When his doctors – including Carl June and David Porter of the University of Pennsylvania in Philadelphia – wrote the protocol for the clinical trial in which Olson was involved, they hoped the genetically modified cells could survive for a month in his body. They knew cancer research could be heartbreaking; they dared not expect a cure.

But more than ten years later, immune cells continue to patrol Olson’s blood and he remains in remission. June is finally ready to admit what Olson suspected all along. “We can now conclude that CAR T cells can actually cure leukemia patients,” June told reporters during a press briefing describing the findings published in Nature February 21.

Tumor Destroyers

CAR-T cell therapies involve removing immune cells called T cells from a person with cancer and genetically modifying them so that they produce proteins — called chimeric antigen receptors, or CARs — that recognize cancer cells. The cells are then injected back into the person, in the hope that they seek out and destroy tumors.

In the years following Olson’s treatment, five CAR-T cell therapies were approved by the United States Food and Drug Administration, to treat leukemias, lymphomas and myelomas. June estimates that tens of thousands of people have received CAR-T cell therapy.

But the therapy is expensive, risky and technically demanding. It remains a last resort, to be used when all other treatments have failed. Despite the success of treatment for Olson, not everyone experiences lasting remission from his cancer. At first, only about 25 to 35 percent of CAR-T cell recipients with chronic lymphocytic leukemia experienced complete remission of their cancer, Porter says. With refinement, that percentage has increased over the years, he says, but some of those initial successes always lead to relapse. Long-term treatment monitoring could reveal clues to factors important to the lasting success of CAR-T cells.

For more than a decade, Porter and his colleagues analyzed CAR-T cells in Olson and another person treated in 2010, tracing the evolution of the cells and looking for any signs of safety issues.

They found that CAR T cells persisted, but the characteristics of the population changed over time. Shortly after the infusion, a large population of T cells called CD8+ cells emerged. These are sometimes called killer T cells and can identify and destroy cells that have unusual proteins, such as cancer cells or cells infected with a virus.

But over the years, a different type of CAR T cell has become dominant. CD4+ T cells can take on a variety of functions in the immune system, but the researchers showed that both study participants had CD4+ cells whose characteristics suggest that they would be able to kill leukemic cells.

Huge impact

Olson and the other participant no longer have any signs of leukemia. It is unclear whether the CAR T cells killed all the leukemic cells soon after their introduction, or whether the cells that continue to patrol are capable of destroying all the leukemia cells before they reach detectable levels.

“The potential impact of CAR T is enormous,” says Nirali Shah, a pediatric hematologist at the US National Cancer Institute in Bethesda, Maryland. This study “gives you proof of concept on the safety of having long-term persistence and integration of T cells in your body.”

It remains to be seen, she adds, how well the findings of these two people with chronic lymphocytic leukemia will translate to other illnesses. Efforts are underway to use CAR-T cell approaches to treat solid tumors, such as prostate tumors and the devastating brain cancer glioblastoma. In January, researchers reported success in using the cells to destroy scar tissue in the heart – an approach that could one day be used to treat cardiac fibrosis.2.

In the years following his treatment, Olson resumed his career in medical diagnostics. He pledged to stay healthy and his son convinced him to run half marathons. “If my cancer was gone, I certainly didn’t want to die of a heart attack,” he says. Eventually, he decided to go public with his recovery story and serve as a mentor to others with cancer.

He tries to give them hope, he says, “If there’s no cure for their cancer today, chances are there’s one around the corner.


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