Research And Grants

A gasmask for CAR-T: Engineering CAR-T cells to endure the high lactic acid tumor environment

CAR-T cell therapy is an immunotherapy that modifies a patient’s own T cells to attack cancer cells, and is FDA-approved for several cancers. In fatal, diffuse midline gliomas (DMG) and other children’s brain tumors, clinical trials have demonstrated that CAR-T cells can shrink tumors. Tumors have a cloud of lactic acid around them preventing lasting penetration of T-cells, including CAR-T cells. Using adult cancer models, scientists have demonstrated that when drugs are used to reduce the lactic acid, the CAR-T cells survive longer in tumors and are less fatigued. Moreover, injecting lactic acid-lowering drugs together with CAR-T cell injections, increases animal survival more than the CAR-T therapy alone.

DMG brain tumors have elevated levels of lactic acid compared to the surrounding healthy brain. Instead of relying on drugs to penetrate into the brain to reduce lactic acid levels, we will directly alter the CAR-T cells, so they cannot absorb lactic acid through their pores. This will make the CAR-T cells insensitive to the lactic acid oozing from brain tumors. All CAR-T cells get genomically altered as part of their production; our adaptable strategy is like gasmask that could be a lifesaving accessory to current CAR-T cells manufactured for clinical trials.