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Archive of posts published in the category: Immune
Apr
4

CAR T Cells: Engineering Immune Cells to Treat Cancer

For years, the foundations of cancer treatment were surgery, chemotherapy, and radiation therapy. Over the last two decades, targeted therapies like imatinib (Gleevec®)  and trastuzumab (Herceptin®) —drugs that target cancer cells by homing in on specific molecular changes seen primarily in those cells—have also cemented themselves as standard treatments for many cancers.

But over the past several years, immunotherapy—therapies that enlist and strengthen the power of a patient’s immune system to attack tumors—has emerged as what many in the cancer community now call the “fifth pillar” of cancer treatment.

A Tipping Point in Clinical Development

A rapidly emerging immunotherapy approach is called adoptive cell transfer (ACT): collecting and using patients’ own immune cells to treat their cancer. There are several types of ACT (see the box below, titled “ACT: TILs, TCRs, and CARs”), but, thus far, the one that has advanced the furthest in clinical development is called CAR T-cell therapy.

Until recently, the use of CAR T-cell therapy has been restricted to small clinical trials, largely in patients with advanced blood cancers. But these treatments have nevertheless captured the attention of researchers and the public alike because of the remarkable responses they have produced in some patients—both children and adults—for whom all other treatments had stopped working.

In 2017, two CAR T-cell therapies were approved by the Food and Drug Administration (FDA), one for the treatment of children with acute lymphoblastic leukemia (ALL) and the other for adults with advanced lymphomas. Nevertheless, researchers caution that, in many respects, it’s still early days for CAR T cells and other forms of ACT, including questions about whether they will ever be effective against solid tumors like breast and colorectal cancer.

The different forms of ACT “are still being developed,” said Steven Rosenberg, M.D., Ph.D., chief of the Surgery Branch in NCI’s Center for Cancer Research (CCR), an immunotherapy pioneer whose lab was the first to report successful cancer treatment with CAR T cells.

But after several decades of painstaking research, the field has reached a tipping point, Dr. Rosenberg continued. In just the last few years, progress with CAR T cells and other ACT approaches has greatly accelerated, with researchers developing a better understanding of how these therapies work in patients and translating that knowledge into improvements in how they are developed and tested.

“In the next few years,” he said, “I think we’re going to see dramatic progress and push the boundaries of what many people thought was possible with these adoptive cell transfer–based treatments.”

A “Living Drug”

CAR T cells are the equivalent of “giving patients a living drug,” explained Renier J. Brentjens, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center in New York, another early leader in the CAR T-cell field.

As its name implies, the backbone of CAR T-cell therapy is T cells, which are often called the workhorses of the immune system because of their critical role in orchestrating the immune response and killing cells infected by pathogens. The therapy requires drawing blood from patients and