A new immunotherapy could target tumor cells that contain unique mutations.
"Our study deals with the central problem in human cancer immunotherapy, which is how to effectively attack common epithelial cancers," Steven A. Rosenberg, M.D., Ph.D., chief of the Surgery Branch in NCI's Center for Cancer Research, said in a National Institute of Health news release. "The method we have developed provides a blueprint for using immunotherapy to specifically attack sporadic or driver mutations, unique to a patient's individual cancer."
Malignant tumors contain genetic alterations that can trigger the production of mutant proteins; the proteins themselves can launch antitumor immune responses. Melanoma tumors contain mutation-reactive immune cells" called tumor-infiltrating lymphocytes (TILs).
In adoptive cell therapy (ACT) medical experts collect the patient's TILs that have the most potent anti-tumor activity and grow them in the lab to produce even larger populations.
In the past researchers were not sure if the immune system could launch an effective response against these mutant proteins or whether that response could be used to develop immunotherapies tailored to the patient.
The researchers looked at the TILS of a patient who suffered from "bile duct cancer that had metastasized to the lung and liver" and was not responding to chemotherapy. The patient was a 43-year-old woman.
The team performed a whole-exome sequencing; they analyzed protein-coded regions of the DNA that could be recognized by the patient's immune cells.
The medical staff transferred 42.4 billion TILs; 25 percent of them were RBB2IP mutation-reactive T lymphocytes, which activate immunity in other cells. The patient was also given four doses of the cancer drug interleukin-2.
After the treatment the patient's lung and liver tumors stabilized, but started to progress again later on. When the disease started up again the patient was given ACT in which 95 percent of the cells were mutation reactive.
"Given that a major hurdle for the success of immunotherapies for gastrointestinal and other cancers is the apparent low frequency of tumor-reactive T cells, the strategies reported here could be used to generate a T-cell adoptive cell therapy for patients with common cancers," Rosenberg said.
