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Researchers at the National Cancer Institute have developed a new approach to immunotherapy that led to the complete regression of breast cancer in a patient who was unresponsive to all other treatments.
Researchers at National Cancer Institute (NCI), part of the National Institutes of Health (NIH), have developed a new approach to immunotherapy that led to the complete regression of breast cancer in a patient who was unresponsive to all other treatments. The findingswere published in Nature Medicineon June 4, 2018.
The new immunotherapy approach is a modified form of adoptive cell transfer (ACT). ACT has been effective in treating melanoma, which has high levels of somatic, or acquired, mutations. However, it has been less effective with some common epithelial cancers, or cancers that start in the lining of organs, that have lower levels of mutations, such as stomach, esophageal, ovarian, and breast cancers, NIH reports.
In an ongoing Phase II clinical trial, investigators are developing a form of ACT that uses tumor-infiltrating lymphocytes (TILs) that specifically target tumor cell mutations to see if they can shrink tumors in patients with these common epithelial cancers. As with other forms of ACT, the selected TILs are grown to large numbers in the laboratory. Then the TILs are infused back into the patient, who has undergone treatment in the meantime to deplete remaining lymphocytes, to create a stronger immune response against the tumor.
“We’ve developed a high-throughput method to identify mutations present in a cancer that are recognized by the immune system,” said Steven A. Rosenberg, MD, PhD, chief of the surgery branch at NCI’s Center for Cancer Research (CCR), in a company press release. “This research is experimental right now. But because this new approach to immunotherapy is dependent on mutations, not on cancer type, it is in a sense a blueprint we can use for the treatment of many types of cancer.”
A patient with metastatic breast cancer came to the trial after receiving multiple unsuccessful treatments, including several chemotherapy and hormonal treatments. To treat her, the researchers sequenced DNA and RNA from one of her tumors as well as normal tissue to see which mutations were unique to her cancer and identified 62 different mutations in her tumor cells.
The researchers then tested different TILs from the patient to find those that recognized one or more of the mutated proteins. TILs recognized four of the mutant proteins and were then expanded and infused back into the patient. She was also given Merck & Co.’s Keytruda (pembrolizumab), which made $3.8 million in 2017 sales worldwide, to prevent the possible inactivation of the infused T cells by factors in the tumor microenvironment. After the treatment, the findings show that all of the patient’s cancer disappeared and has not returned after more than 22 months.
“This is an illustrative case report that highlights, once again, the power of immunotherapy,” said Tom Misteli, PhD, director of CCR at NCI, in the release. “If confirmed in a larger study, it promises to further extend the reach of this T-cell therapy to a broader spectrum of cancers.”
According to NIH, investigators have seen similar results using mutation-targeted TIL treatment for patients in the same trial with other epithelial cancers, including liver cancer and colorectal cancer. Rosenberg explained that results like this in patients with solid epithelial tumors are important because ACT has not been as successful with these kinds of cancers as with other types that have more mutations.
Rosenberg noted that the “big picture” here is that this kind of treatment is not cancer-type specific. “All cancers have mutations, and that’s what we’re attacking with this immunotherapy,” Rosenberg added in the release. “It is ironic that the very mutations that cause the cancer may prove to be the best targets to treat the cancer.”