New culture method boosts T cells' ability to recognize multiple cancers

Human T cell
Mayo Clinic and University of Washington scientists have developed a new culture method to grow T cells that recognize and target many cancers. Image: NIAID

Engineered T cells, which aim to mount an immune response against cancer, are gaining steam in the immuno-oncology market, with Kite Pharma and Novartis racing to get their CAR-T therapies for blood cancers approved. But they don't work for all patients, and researchers have struggled to find uses for them in solid tumors.

Now researchers from Mayo Clinic and the University of Washington have developed a new process to improve the efficacy of these treatments.

The immune system identifies tumors—uncontrolled cell growth—as “self,” so it can be challenging to provoke an immune response against cancer. In CAR-T therapy, T cells are taken from patients and modified to express chimeric antigen receptors to target specific cancers. This allows the T cells to recognize the patients' specific tumor cells and target them for destruction.

But the method has its challenges, including “achieving robust expansion” of tumor-specific T cells from blood, the researchers wrote in their study, which was published in Oncotarget. The researchers’ new culture method could improve the ability of engineered T cells to recognize cancer cells.

“Even though it is relatively easy to collect billions of T cells directly from patient blood, it has historically proved difficult or impossible to unleash those T cells’ natural ability to recognize and target cancer cells,” says Peter Cohen, M.D., a Mayo Clinic immunotherapist, in the statement.

In a two-step process, the team exposed the T cells to cancer-related proteins, which activated innate immunity. They also replicated signals that normally occur in the body when a serious infection is present—alarm bells, if you will, that awaken resting T-cells and prompt them to multiply.

“Our method strictly employs natural signals to activate the immune blood cells outside the body,” said Nora Disis, M.D., a University of Washington immunotherapist. “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.”

They studied the culture method’s ability to produce T-cell responses against the proteins MUC1, HER2/neu and CMVpp65. MUC1 is expressed in multiple cancers, including breast, pancreatic and lung, among others. HER2/neu is present in as many as half of a range of cancers and CMVpp65 is expressed by half of primary brain tumors, according to the statement.

The researchers found that it took three weeks to raise “natural T-cell armies” trained to recognize cancers that express these proteins. And they’re not stopping here: the team thinks the method could be applied to other proteins that are present on cancer cells.

Expanding the utility of T-cell treatments beyond blood cancers is a major focus among immuno-oncology researchers. Kite, for example, is in early-stage trials of several novel T-cell treatments for solid tumors. And the University of Pennsylvania, which is partnered with Novartis on CAR-T work, reported progress last year on its own next-generation CAR-T that they hope will show promise in solid tumors.