Immunotherapies using engineered T cells have ushered in a new era in cancer treatment, but they have their limits. They may cause side effects or stop working, and they do not work at all against 90% of cancers.
Now, scientists at UC San Francisco and Northwestern Medicine may have found a way around these limitations by borrowing a few tricks from cancer itself.
By studying mutations in malignant T cells that cause lymphoma, they zeroed in on one that imparted exceptional potency to engineered T cells. The team inserted a gene for this unique mutation into normal human T cells, which made them more than 100 times more potent at killing cancer cells. They kept the tumors at bay for many months, showing no signs of becoming toxic.
While current immunotherapies work only against cancers of the blood and bone marrow, the new approach was able to kill solid tumors derived from skin, lung and stomach tissues in mice. The team has already begun working toward testing this new approach in people.
The breakthrough was inspired by the martial arts principle of using an opponent’s strength against them, said Kole Roybal, PhD, a co-author on the study and associate professor of microbiology and immunology.
“We’ve used the mutations that give cancer cells their staying power to engineer what we call a ‘Judo T-cell therapy’ that can survive and thrive in the harsh conditions that tumors create,” he said.