A new study has shown how personalized cell-based immunotherapy can be effective at treating ovarian cancer which is often resistant to non-tailored immunotherapy treatments. The study focused on a specific type of T cell called tumor-infiltrating lymphocytes (TILS), which are located inside tumors instead of in the bloodstream. The study showed that, when isolated and enriched, TILs were much better at recognizing and killing cancer cells than T cells circulating in the bloodstream. The study was published in Nature Communication.
Many types of tumor cells, such as in melanoma and lung cancer, are highly mutated and it’s been demonstrated that immunotherapy is most effective at treating cancers with a large number of mutations. "It has long been a question whether we'd even be able to detect sufficiently mutation-reactive T cells in patients with tumors that have low mutational loads,” Alexandre Harari co-leader of the study.
Killer T cells recognize neoepitopes, small pieces of an antigen expressed on cancer cells, and destroy the cell. Experimental immunotherapies where T cells are isolated from an individual’s bloodstream and enriched for those that are most specific to the cancer have been successful. However, therapies using T cells from the bloodstream haven’t worked well in fighting solid tumors. The researchers developed a protocol for enriching highly reactive TILs and compared their activity to their counterparts isolated from the bloodstream. They demonstrated in experiments that TILs from ovarian tumors were much better at targeting the same mutation compared to circulating T cells. In addition, using their newly developed method, the research team was able to successfully isolate highly reactive TILs from 90 percent of ovarian cancer patient tumor samples they received.
"The big message," says Coukos, "is that future cell-based therapies can be envisioned for low mutational load tumors and should prioritize the use of TILs over T cells collected from peripheral blood. This novel strategy to obtain enriched TILs also offers great therapeutic opportunities."