Researchers at the University of Southampton have developed multi-pronged antibodies designed to better activate the body’s cancer-killing T cells.
The study, published in Nature Communications, outlines how these specially engineered antibodies work by clustering immune cell receptors, enhancing the signal that triggers T cells to attack cancer cells.
The team focused on an immune receptor called CD27, which requires a matching ligand to fully activate T cells.
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A microscopy image depicting immune receptor distribution analysis in human T cells. (Image: University of Southampton)
While this ligand is naturally produced during infection, cancers lack this signal, resulting in only a weak immune response.
Professor Aymen Al-Shamkhani, who led the study, said: “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.”
Standard antibodies are Y-shaped with two prongs, limiting them to engaging just two receptors at once.
The new antibodies have four prongs, allowing them to latch onto more receptors.
They also recruit another cell, causing all the CD27 receptors they bind to cluster together, which strengthens the activation signal.
This method mimics how CD27 is naturally activated in the immune system.
In laboratory tests using mice and human immune cells, the multi-pronged antibodies were more effective than standard antibodies at activating CD8+ T cells, the ‘special forces’ of the immune system.
This led to a stronger anti-tumour response.
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Professor Al-Shamkhani said: “This approach could help improve future cancer treatments by allowing the immune system to work closer to its full potential.”
The findings offer a potential blueprint for developing next-generation immunotherapies that more effectively harness the immune system to fight cancer.
The research was funded by Cancer Research UK and highlights the University of Southampton’s Centre for Cancer Immunology.
The full study, titled ‘Harnessing Multivalency and FcγRIIB Engagement to Augment Anti-CD27 Immunotherapy,’ was published in Nature Communications.