Adaptive immunotherapy, or the rapid expansion of a patient’s immune cells in a petri dish, is a promising strategy for cancer patients, but one that faces significant barriers, particularly in the expansion of natural tumor-reactive T-cells.
But researchers have now discovered a new culture method that allows the growth of natural T-cells trained to recognize cancer cells expressing a certain protein within just three weeks.
The study, “Surrogate in vitro activation of innate immunity synergizes with interleukin-7 to unleash rapid antigen-driven outgrowth of CD4+ and CD8+ human peripheral blood T-cells naturally recognizing MUC1, HER2/neu and other tumor-associated antigens,” was published in Oncotarget.
“Even though it is relatively easy to collect billions of T-cells directly from patients’ blood, it has historically proved difficult or impossible to unleash those T-cells’ natural ability to recognize and target cancer cells,” Peter Cohen, MD, a Mayo Clinic immunotherapist, said in a news release.
Cohen co-led the study with Mayo Clinic immunologist Sandra Gendler, PhD, and University of Washington immunotherapist Nora Disis, MD.
The researchers found that T-cells traveling within the bloodstream remain in a resting state unless they receive a signal that is normally triggered by serious infections. Therefore, they hypothesized that the expansion of T-cells recognizing a specific antigen could be better triggered by providing signals that mimicked a life-threatening infection.
“Our method strictly employs natural signals to activate the immune blood cells outside the body,” Disis said. “This gives rise to expanded armies of T-cells, which specifically recognize proteins that are present on cancer cells and which can be reinfused into patients for therapeutic evaluations in future clinical trials.”
The team was able to effectively stimulate T-cell responses against cells expressing MUC1, a protein that is found in a vast number of cancer types, including breast, lung, pancreatic, ovarian, kidney, bladder, and colorectal cancers, as well as multiple myeloma. They could also promote expansion of T-cells targeting the tumor-promoting proteins HER2, found in 25% to 50% of all cancers, and CMVpp65, which is expressed in half of primary brain tumors.
“Our culture method is similar to performing a vaccination procedure entirely outside the body, and it was successful for all three proteins,” Gendler said.
The three proteins cover most human cancers, but the researchers believe that the method could be extended to other cancer proteins, covering a larger number of cancer types.
“The cancer-associated proteins we have tested so far already target the majority of human cancers, and it is likely that this culture method will extend to many additional proteins present on cancer cells,” Gendler said.
“We are pleased to help other investigators implement our culture method for their own cancer-associated proteins of interest,” Cohen added.