Tumor-derived T cells show promise against ovarian cancer

Human T cell
Blood-derived T cell therapies have had limited success against solid tumors. Using tumor-infiltrating lymphocytes may solve this problem in ovarian tumors. (Image: NIAID)

Engineered T cell treatments, based on immune cells taken from a patient's own blood, have seen success in blood cancers, but are harder to deploy against solid tumors. Part of the problem is that many tumors don't have enough mutations that would alert the immune system to the presence of cancer. Extracting T cells directly from tumors, growing them in culture and then putting them back into the patient could be an effective alternative.

A team of scientists from the Ludwig Institute for Cancer Research in Lausanne, Switzerland, found that epithelial ovarian tumors contain T cells that are particularly good at identifying and killing cancer cells. Extracting these tumor-infiltrating lymphocytes (TILs) and expanding them for reinfusion into patients is not a new idea, but previous attempts have come up empty. The proportion of the "juiciest" T cells—those that recognize mutations on cancer cells—tends to drop when the cells are grown in culture, said Alexandre Harari, a scientist at the Ludwig Lausanne Branch, in a statement. 

So the Ludwig team developed a new technique to identify "highly reactive" TILs and grow them in a way that enriches them instead of diluting them.  Then they compared the activity of TILs that target neoepitopes, which are the mutated segments of antigens that alert the immune system to cancer, with that of T cells taken from blood. 

The team found that the engineered killer TILs from ovarian tumors were much better at pinpointing neoepitopes than their blood-derived counterparts. And that's not all—they were able to find highly reactive killer T cells in about 90% of the ovarian cancer patients they studied, suggesting that such a therapy would be widely applicable. The study is published in Nature Communications. 

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Several research groups and biotech companies are searching for ways to treat solid tumors with engineered immune cells. Lion Biotechnologies and the University of Texas MD Anderson Cancer Center, for example, are working on a TIL approach in a pancreatic cancer and various sarcomas, as well as in ovarian cancer. The pair inked a deal last April to perform preclinical work in rare tumor types on top of running clinical trials testing the former's TIL therapy. And a team from the University of North Carolina is homing in on a new CAR-T target that could make the treatment more effective for glioblastoma, the most aggressive of brain tumors.

The next step for the Ludwig team will be to apply their findings to a broader program underway at the cancer center to develop personalized treatments for patients.

"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 George Coukos, director of the Ludwig Institute for Cancer Research, Lausanne. "This novel strategy to obtain enriched TILs also offers great therapeutic opportunities."