A new immunotherapy method that targets a patient’s tumor cell mutations led to a complete and lasting regression of breast cancer in a woman who had failed all other treatments, a study reported.
The woman, whose disease already had spread to other organs, was free from cancer more than 22 months after receiving the therapy.
The study, “Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer,” was published in the journal Nature Medicine.
The new immunotherapy approach, developed by researchers from the National Cancer Institute (NCI) Surgery Branch, consists of a modified version of autologous adoptive cell transfer — the transfer of a patient’s own cells after they have undergone some kind of treatment or modification.
Adoptive transfer of anti-tumor lymphocytes — white blood cells capable of recognizing and killing cancer cells — has shown effectiveness in treating cancers with high levels of mutations, including melanoma, smoking-induced lung cancers, and bladder cancer.
However, to date, this approach has been unsuccessful for treating other types of cancer with lower mutation rates, such as those arising in the gastrointestinal tract, breast, and ovary.
But researchers developed a way to target tumors even when their mutations rates are low.
“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 NCI’s Center for Cancer Research and a senior author of the study, said in a press release.
The patient described in the study was a 49-year-old woman with hormone receptor (HR)-positive metastatic breast cancer, resistant to multiple chemotherapy and hormone treatments.
The woman participated in a Phase 2 clinical trial (NCT01174121), that is evaluating the new immunotherapy against several types of metastatic cancer, including breast, brain, digestive tract, urothelial, and ovarian cancers.
The new method involves taking white blood cells from the patients’ tumors, called tumor-infiltrating lymphocytes (TILs), growing them in the laboratory in large numbers, and then infusing them back into the patient.
The novelty is that the patient’s lymphocytes — in particular T cells — are selected in the laboratory to specifically recognize and kill the patient’s’ own cancer cells, an approach more likely to be effective to fight the tumor.
To do that, researchers first have to identify which mutations are specific to a patient’s tumor, and not present in the their normal tissues, which they do by using advanced sequencing technology.
After identifying these tumor-specific mutations, researchers are able to spot the proteins corresponding to those mutations that also are unique to the patient’s tumor.
Using them as “bait” they select lymphocytes highly specific to the patients’ tumor, which are then expanded and infused back into the patient.
The woman also was treated before infusion with a regimen to deplete the remaining lymphocytes and boost the anti-tumor immune response, and after the infusion with Keytruda (pembrolizumab) to prevent potential inactivation of the infused lymphocytes.
The new immunotherapy gave striking results. After the treatment, the patient’s cancer dropped to undetectable levels in all organs affected (chest, armpit, and liver). All metastasis had resolved one year after the adoptive lymphocyte transfer and have not returned for more than 22 months.
“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,” Rosenberg said.
“All cancers have mutations, and that’s what we’re attacking with this immunotherapy,” he added.