A tweaked version of a cellular immunotherapy that recognizes mutations in a patient’s tumor has led to the complete regression of metastatic breast cancer in a woman whose disease had failed to respond to multiple lines of chemotherapy, a study reports.
The therapy is being tested in a Phase 2 clinical trial (NCT01174121) at the National Institutes of Health in Maryland, which is currently enrolling patients with various advanced cancers. More information is available on the trial’s official page.
The results were published in the the journal Nature Medicine in a study titled, “Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer.”
Autologous adoptive cell transfer is a personalized cancer therapy that uses a patient’s own immune cells, which are cultured and expanded outside the body, and then reintroduced into the patient.
While this therapy has shown positive results in cancers with a high burden of mutations — like melanoma, a type of skin cancer — the therapy has led to shy outcomes in cancers with a lower mutation level, like epithelial cancers – a category that includes breast, stomach, esophageal, and ovarian cancers.
The 49-year-old breast cancer patient had failed to respond to several rounds of chemotherapy and hormonal therapy when she joined the Phase 2 clinical trial, at the National Health Institute (NHI).
Researchers extracted DNA and RNA from one tumor lesion on her right breast, as well as from normal tissue, and screened the genetic material for mutations that were unique to her cancer.
After detecting 62 mutations in her tumor cells, and identifying the corresponding proteins, researchers extracted immune cells from the patient’s tumor – called tumor infiltrating lymphocytes (TILs) – to see if her immune cells could recognize any of the mutated proteins.
She had subsets of immune cells that were specific to four of these proteins. These subsets were then expanded in the lab and injected back into her bloodstream. Keytruda (pembrolizumab, by Merck) was also given to prevent immune cell inactivation.
In total, the patient received 80,000 million cells, given in seven injections. Six weeks after the last infusion, her tumor size dropped by 51 percent, and continued to decline until no traces of cancer were detected on imaging scans. This included her breast tumor and metastatic lesions in the chest and liver. Cancer regression is ongoing for more than 22 months, the study reports.
“We’ve developed a high-throughput method to identify mutations present in a cancer that are recognized by the immune system,” Steven A. Rosenberg, MD, PhD, chief of the surgery branch at National Cancer Institute (NCI) Center for Cancer Research (CCR) and the study’s lead author, said in a 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,” he added.
Similar outcomes are being seen in patients with other epithelial cancers, including liver cancer and colorectal cancer.
“All cancers have mutations, and that’s what we’re attacking with this immunotherapy,” Rosenberg said. “It is ironic that the very mutations that cause the cancer may prove to be the best targets to treat the cancer.”
