Antibody-drug conjugates pair a tumor-killing drug with an antibody that seeks out a specific marker on cancer cells, and they are often reserved for patients whose standard chemotherapy has stopped working. Their precision comes with a built-in ceiling: each one recognizes a single target. Researchers at Washington University School of Medicine in St. Louis report that they have found a way around that limit, at least in mice, by re-engineering existing FDA-approved versions of these drugs so that they link up inside the body and go after more than one cancer target at a time.
The team's approach relies on self-assembly. Rather than manufacturing a complex dual-targeting molecule from scratch, the modified antibodies bind to one another after they are administered. "We've shown that when two cancer-targeting antibodies bind together inside the body, they accumulate at the tumor more effectively and improve treatment response," said Patricia M. Ribeiro Pereira, PhD, assistant professor of radiology at the WashU Medicine Mallinckrodt Institute of Radiology and a research member of Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine.
Why this matters comes down to how tumors change. As a cancer progresses or adapts around conventional treatment, it is increasingly likely to carry several different target proteins at once - which is exactly the situation in which a single-target drug loses ground. A therapy that engages two targets simultaneously could keep working where the current generation stalls.
The work was done in mice, and the results describe better tumor accumulation and treatment response in that model rather than benefit in patients. Still, building on drugs that already have FDA approval is a practical starting point, since the underlying components have cleared regulatory review for human use.