New Strategy May Improve T-Cell Therapy in Solid Tumors
Since their discovery, personalized cellular therapies have revolutionized blood cancer treatment, but remain ineffective against solid tumors—largely due to the loss of inflammatory effector functions.
The lab of CAR T cell pioneer Carl June, MD, professor in immunotherapy at the Perelman School of Medicine, University of Pennsylvania, explores strategies to improve T-cell therapies for solid tumors. Their latest study shows that targeting two inflammatory regulators delivered a “one-two punch” that led to at least 10 times greater T-cell expansion in preclinical models.
More specifically, the researchers targeted a regulatory axis of T-cell inflammatory responses, Regnase-1 and Roquin-1, to “enhance antitumor responses in human T cells engineered with two clinical-stage immune receptors.” The findings show that a knockout of either Regnase-1 or Roquin-1 alone enhances antitumor function in solid tumor models. But the double knockout increases function more than either one alone.
“We want to unlock CAR T cell therapy for patients with solid tumors, which include the most commonly diagnosed cancer types,” said June. “Our study shows that immune inflammatory regulator targeting is worth additional investigation to enhance T-cell potency.”
This work is published in PNAS in the paper, “Combined disruption of T cell inflammatory regulators Regnase-1 and Roquin-1 enhances antitumor activity of engineered human T cells.”
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