A new method that identifies and expands T-cells with high tumor-killing activity is a promising approach against ovarian cancer, a study shows.
Findings could be used to develop a personalized, cell-based immunotherapy that effectively treats ovarian cancer, which has proven resistant to current immunotherapies.
Using this method, researchers found that T-cells that are isolated from tumors have better anti-cancer properties than their counterparts isolated from the bloodstream.
The study, “Sensitive and frequent identification of high avidity neo-epitope specific CD8+ T cells in immunotherapy-naive ovarian cancer,” was published in the journal Nature Communications.
Tumors with cells that are highly mutated are usually more responsive to immunotherapies because the rate of mutations in these tumors leads to the formation of abnormal, mutated proteins — neoantigens – that may be recognized by the immune system.
A subset of effector immune cells called CD8 T-cells can recognize small pieces of neoantigens — called neopitopes — as foreign and orchestrate an immune attack against the cancer cells.
The amount of neoepitopes exposed to the immune system, however, varies greatly among patients, even those with the same cancer type. This has impaired the development of antigen-targeting therapies, or immunotherapies.
Tumor cells in patients with epithelial ovarian cancer have a low mutational burden that further inhibits the development of such therapies.
To overcome these limitations, researchers are developing new methods to isolate tumor-killing T-cells from patients and expand them in the lab. They can then reinfuse the anti-tumor T-cells in high numbers back into the patients.
T-cells are usually collected from a patient’s blood instead of those already in the tumor, which are known as tumor-infiltrating lymphocytes, or TILs.
However, circulating T-cells in the bloodstream are also usually less effective at killing solid tumors, and the anti-tumor activity of the “juiciest” TILs, or those that can recognize mutations on cancer cells, tends to decline when they are expanded in the lab.
“To circumvent these problems, we developed a new methodology to identify highly reactive TILs and expand them in a manner that, rather than diluting the juiciest TILs, enriches them instead,” Alexandre Harari, PhD, investigator at the Ludwig Institute for Cancer Research in Switzerland and the study’s co-lead author, said in a press release. “This allowed us to compare the activity of TILs that target neoepitopes with their counterparts in the peripheral bloodstream.”
Researchers showed that T-cells isolated from ovarian tumors using their new method are much more effective at recognizing neoepitopes than T-cells from the blood.
“We could even compare T cells from the two compartments targeting the exact same mutation and show that the TILs were more functional than the T cells we collected from the peripheral bloodstream,” Harari said.
With their new method, researchers were able to obtain T-cells with high anti-tumor killing activity from 90% of the ovarian cancer patients they tested.
“The big message 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,” said co-lead author George Coukos, MD, PhD, director of the Ludwig Institute for Cancer Research. “This novel strategy to obtain enriched TILs also offers great therapeutic opportunities.”
Findings support previous evidence that ovarian cancers are susceptible to immune recognition. The next step is to develop a personalized immunotherapy program for cancer patients at the Ludwig Institute for Cancer Research.