Researchers at the University of Southampton have created a new class of antibodies designed to strengthen the immune system's attack on cancer cells. These antibodies cluster receptors on T cells to amplify activation signals that tumors typically weaken. Early laboratory tests indicate they outperform standard antibodies in mobilizing cancer-killing immune cells.
Scientists at the University of Southampton's Centre for Cancer Immunology have pioneered a strategy to bolster the immune response against cancer by engineering antibodies with four binding arms. Traditional antibodies, shaped like a Y with two arms, can only bind two receptors at a time, limiting their effectiveness in fully activating T cells. In contrast, the new design attaches to multiple CD27 receptors simultaneously and recruits another immune cell to cluster them, mimicking the body's natural activation during infections.
CD27 is a key receptor on T cells that requires a specific ligand to trigger a strong response. While infections provide this ligand, cancer cells do not, resulting in weak signals that hinder T cells from effectively targeting tumors. The enhanced antibodies address this by intensifying the signal, pushing CD8+ T cells—known for their direct destruction of cancer cells—into heightened activity.
Professor Aymen Al Shamkhani, who led the research, explained: "We already understood how the body's natural CD27 signal switches on T cells, but turning that knowledge into a medicine was the real challenge. Antibodies are reliable molecules that make excellent drugs. However, the natural antibody format was not powerful enough, so we had to create a more effective version."
Tests on mice and human immune cells demonstrated superior activation of CD8+ T cells compared to conventional antibodies, leading to a more robust anti-tumor response. Professor Al Shamkhani added: "This approach could help improve future cancer treatments by allowing the immune system to work closer to its full potential."
The study, published in Nature Communications, was funded by Cancer Research UK and provides a foundation for advancing immunotherapy options.
