Package for you

This cover illustrates an article that looks at a new way to make cancer antibody drugs work better by getting them inside cancer cells and reach the cell’s recycling compartment, where the toxic drug they carry is released. The team attached a small peptide that helps the antibody–drug package move into cells, and they tested this approach on several cancer targets and drug payloads.

They were trying to fix a common problem: some cancer targets bind well to antibodies but do not pull those antibodies into the cell fast enough for the drug to do its job. By adding this extra peptide, they made the drug packages enter cells more efficiently, which increased cell killing in lab tests, in 3D tumor-like models, and in mice.

One of the most striking results was with a CA9-targeting antibody that on its own did almost nothing in cell culture, but became strongly active once the peptide was added. This design could turn some previously hard-to-treat cancer markers into workable targets for antibody-drug therapy, which broadens the number of cancers these drugs might address.