A newly developed multi-pronged antibody design may enable immune cells to receive more powerful activation signals to better target cancer.
Scientists at the University of Southampton have discovered a new approach that may enhance the immune system’s ability to fight cancer.
Engineered Antibodies Boost T Cell Activation
In a study published in Nature Communications, the researchers report on the development of specially engineered antibodies that are better able to activate T cells responsible for killing cancer cells.
These antibodies work by simultaneously binding to and clustering multiple immune cell receptors, amplifying the signal that tells T cells to attack tumors.
The study, led by the University of Southampton’s Centre for Cancer Immunology, focused on the CD27 immune receptor. For T cells to become fully activated, CD27 must bind to a specific matching ligand. While this ligand is naturally produced during infections, it is largely missing in cancer. Without this signal, T cells are weakly activated and struggle to fight cancer cells.
Limitations of Traditional Antibodies
Antibodies can unlock immune receptors, but most therapies use Y-shaped antibodies with only two binding sites. As a result, they can interact with just two receptors at once.
While antibody treatments have revolutionized cancer therapy, they do not work for everyone. In many patients, T cells do not receive all the necessary activation signals required to become fully effective.
The researchers engineered antibodies with four binding sites to attach to more receptors simultaneously. These antibodies also draw in a second cell, causing the attached CD27 receptors to cluster together. This clustering boosts the activation signal and closely mimics the way CD27 is naturally activated in the body.
Professor Aymen Al-Shamkhani said the challenge was turning CD27’s T cell activation into a therapy. Antibodies are reliable drugs, but the standard form wasn’t strong enough, so a more powerful version was needed.
Enhanced Anti-Tumor Responses
In laboratory experiments with both mice and human immune cells, the new antibodies proved more effective at activating CD8⁺ T cells—the immune system’s “special forces”—compared to conventional Y-shaped antibodies, resulting in a stronger anti-tumor response.
By enhancing CD27’s responsiveness to treatment, the study offers a framework for creating next-generation immunotherapies that more effectively mobilize the immune system against cancer.
Professor Al-Shamkhani commented: “This strategy could strengthen future cancer therapies by enabling the immune system to operate closer to its full capacity.”
Read the original article on: SciTechDaily
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