Engineering Enhanced Gamma Delta T-Cells to Overcome DIPG Immune Resistance

My research focuses on a unique type of immune cell called a gamma delta T cell. Unlike conventional T cells, which rely on HLA molecules—the body’s cellular “ID cards”—to identify threats, gamma delta T cells recognize stress signals that cancer cells struggle to hide. This is especially important in DIPG, where tumors often reduce HLA expression specifically to evade immune detection. Gamma delta T cells can see through that disguise.
I then engineer these cells further, equipping them with chimeric antigen receptors, or CARs. These synthetic receptors act like molecular GPS systems, directing immune cells toward specific proteins found on tumor cells. Traditional CAR-T therapies typically target a single protein, which can be effective until the tumor adapts and stops expressing that target. When that happens, the therapy loses its ability to recognize the cancer. Our approach is designed to make escape more difficult.

Instead of targeting one protein, we engineer cells to recognize two tumor-associated proteins simultaneously: B7-H3 and HER2. Both are highly expressed in DIPG and largely absent from healthy brain tissue. If a tumor loses one target, the engineered cell can still recognize the other, maintaining its ability to attack the cancer. At the same time, I use multiplex genome-editing tools to reprogram the cells internally, reducing the molecular signals that cause immune exhaustion within the tumor microenvironment. The goal is not only precision, but persistence—immune cells engineered to keep fighting long after conventional cells would have stopped.