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T cells have a built-in off switch called PD-1 that stops them attacking the body's own tissue. Many tumours exploit it, pressing the switch to shut down the immune cells that come after them. Cancer drugs block the switch chemically; gene editing removes it from engineered cells altogether.
PDCD1, at 2q37.3, encodes programmed cell death protein 1, an inhibitory receptor whose engagement by PD-L1 attenuates T-cell activation. Checkpoint inhibitor antibodies block this axis pharmacologically; PDCD1 knockout removes it permanently from engineered T cells. It was among the genes edited in the first US CRISPR-engineered T-cell trial in 2020.
Sources
- Science (Stadtmauer et al.) · 2020
CRISPR-engineered T cells in patients with refractory cancer ↗