One of the most promising cancer therapies to emerge in recent years is CAR T-cell therapy. This genetically alters a patient’s white blood cells, or T cells, to target a specific protein, or antigen, found on the surface of cancer cells before releasing chemicals to kill them. The problem is that cancer cells often share antigens with cells of other types, so the therapy is currently limited to cancers of certain blood cells with unique antigens.
Marc Lajoie has invented a way to reprogram T cells so they can target combinations of antigens rather than just single ones, which should allow them to tackle a much wider range of cancers. “It’s the equivalent of putting a microchip into a cell,” he says. “We can install these new programs and co-opt the cell to make the decisions that we want them to make.”
“We can install these new programs and co-opt the cell to make the decisions that we want them to make.”
Lajoie and colleagues at the University of Washington developed switches made from proteins, which he then used as the basis of a series of logic gates capable of carrying out the same “and,” ”or,” and “not” operations that computer chips do.
Such gates can be tuned to react to different antigens, which allows T cells to target unique combinations of antigens, avoid antigens found on healthy cells, or target cancers that develop resistance due to antigen loss.
Lajoie has cofounded a startup called Lyell Immunopharma and works at the company’s Seattle office to develop more effective CAR T-cell therapies using his protein logic. But he says the same technology could help treat all kinds of diseases by rewiring how cells respond to their environment.