After undergoing an experimental genetic treatment, a woman with advanced pancreatic cancer saw her tumors shrink by 72%— highlighting a potential new way to treat a variety of solid cancer tumors.
Key takeaways: Defining and assessing value for next-generation therapies
In CAR-T cell therapy, providers remove a type of immune cell called T cells from a patient's blood, genetically modify them with receptors that target and destroy cancer cells, and then infuse the T cells back into the patient's blood.
Although these therapies are promising treatments for certain cancers, such as blood cancers, the treatment has not yet worked in patients who have solid tumors, such as the ones found in individuals with breast or prostate cancer.
Now, an experimental treatment using a similar method may be able to treat solid cancer tumors. The treatment, which is called T cell receptor, or TCR, therapy, modifies T cells to detect specific gene mutations in cancer cells.
The technique, which was developed by Eric Tran and Rom Leidner, both researchers at the Earle A. Chiles Research Institute, which is part of the Providence Cancer Institute, modifies T cells to specifically target KRAS, a mutated protein. This mutated protein is found 25% of all cancers, including a third of lung cancers, 40% of colon cancers, and around 95% of pancreas cancers. In addition, the modified T cells will only attack cancer cells while leaving healthy cells alone.
According to Robert Vonderheide, a pancreatic cancer specialist and director of the University of Pennsylvania's Abramson Cancer Center, the mutated KRAS gene "is such a bull's-eye" that being able target cells with the mutation would have "major implications" for cancer treatments.
So far, TCR therapy has been tested in two patients with advanced pancreatic cancer, which is often difficult to treat. Although one patient did not respond to the treatment, the other patient, Kathy Wilkes, a 71-year-old woman, saw significant improvements.
Wilkes, who was originally diagnosed with pancreatic cancer in 2018, had undergone chemotherapy, surgery, and radiation to remove her tumors, but her cancer then metastasized in her lungs. After further chemotherapy and radiation, as well as an experimental immunotherapy treatment, all failed to help her lung metastases, so Wilkes went to Tran and Leidner to try TCR therapy.
Six months after her treatment, Wilkes' tumors had shrunk by 72%, and while her cancer is not yet cured, recent checkups suggest that her disease is now stable. "We are cautiously optimistic," she said.
Josh Veatch, a physician at the Fred Hutchinson Cancer Research Center, said the results of Wilkes' treatment are "really exciting," adding that this is "the first time this sort of treatment has worked in a very difficult-to-treat cancer type."
Last Wednesday, a report of Wilkes' successful treatment with TCR therapy was published in the New England Journal of Medicine (NJEM). According to Eric Rubin, NJEM's editor-in-chief, the proof-of-concept experiment with TCR therapy is "an important step along the way" to developing similar treatments for lung, colon, and other cancers.
In addition, Rubin said TCR therapy may potentially be able to target multiple cancer-causing mutations at once. "We're talking about the chance to distinguish tumor cells from non-tumor cells in a way that we never could before," he said.
Although Tran emphasized that TCR therapy is still highly experimental, he said that Wilkes' successful treatment "provides me with optimism that we're on the right track." Currently, Tran and his team are working to further study and test the treatment using "hot-spot" mutations to target certain cancer cells. (Kolata, New York Times, 6/1; Neergaard, AP/STAT News, 6/1)
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