Researchers at Washington University School of Medicine in St. Louis announced on July 15 that they have developed a new approach to improve the effectiveness of antibody-drug conjugates for cancer treatment. These modern anticancer medications, typically used when standard chemotherapy has failed, are designed to target specific proteins on cancer cells but usually attack only one type of receptor at a time. This limitation reduces their efficacy against tumors with multiple types of targets, which is common as cancers progress or become resistant to therapy.
The team modified existing U.S. Food and Drug Administration-approved antibody-drug conjugates so that they self-assemble inside the body and can attack more than one cancer cell receptor simultaneously. The results, published in Nature, showed dramatic improvements in the effectiveness of these medications in mouse models.
"There is a lot of excitement here because we have shown that it isn't necessary to create a whole new drug platform for each therapeutic target," said Ribeiro Pereira. "We can repurpose antibodies that already exist to improve treatments."
The researchers used click chemistry—a method allowing molecules to snap together like building blocks—to create a modular system where an additional antibody could be attached if needed. This allowed their experimental drugs either to double up on attacking one receptor or simultaneously target two different receptors found within complex tumors.
Testing this approach in mice with pancreatic, gastric, or breast cancers expressing EGFR and HER2 receptors led to higher drug uptake by tumor cells and improved survival rates compared with standard treatments. In the pancreatic model, up to 90% of animals survived 120 days after treatment using the new form versus less than 80 days on average with traditional drugs.
Ribeiro Pereira said the technique could potentially treat various tumor types and other diseases difficult to address with conventional medicine due to its adaptability and speed—linking molecules take just one to three days to manufacture. "We're trying to optimize this tool to help antibodies reach tumors that are normally very difficult to treat, such as brain tumors," Ribeiro Pereira said. "It's exciting, because the drug development process doesn't need to start from the beginning—we can use drugs that are already FDA-approved, which could help bring improved treatments to the clinic more quickly. At the same time, the approach is flexible enough to be adapted to new cancer targets as we learn more about what drives treatment resistance."
