For more than two decades, Timothy Lu, MD, PhD, has been dedicated to a problem that has vexed cell therapy since its inception: how to make engineered cells “smart” enough to distinguish cancer from healthy tissue. In the CAR T era, many of the most transformational therapies have targeted a handful of “clean” antigens—molecules expressed on tumor cells but rarely found on healthy ones. But most cancers don’t present such tidy molecular bull’s-eyes. When healthy tissues share the same markers, CAR T cells can destroy not only tumors but also the cells patients need to survive. The resulting toxicities have kept entire classes of malignancies, especially acute myeloid leukemia (AML) and most solid tumors, out of reach.

Now, Lu—a synthetic biologist, physician, and former MIT professor tur

See Full Page