University of Southampton Researchers Develop Enhanced Antibody Strategy to Boost Cancer Immunotherapy

microscopy image depicting immune receptor distribution analysis in human T cells. The same-coloured spots represent receptors that are clumped together in a single cluster.

(IN BRIEF) Researchers at the University of Southampton have developed a new antibody design that boosts the immune system’s ability to fight cancer by enhancing activation of T cells through the CD27 receptor. Published in Nature Communications, the study shows that four-pronged antibodies can cluster immune receptors more effectively than conventional antibodies, leading to stronger anti-tumour responses and offering a promising blueprint for future cancer immunotherapies.

(PRESS RELEASE) SOUTHAMPTON, 8-Jan-2026 — /EuropaWire/ — University of Southampton researchers have developed an innovative antibody-based strategy that could significantly strengthen the immune system’s ability to recognise and attack cancer cells. The findings, published in Nature Communications, outline a new approach to activating cancer-killing T cells by enhancing key immune signals that are often absent in tumours.

Led by scientists at the University of Southampton’s Centre for Cancer Immunology, the research focuses on improving how T cells receive activation signals through an immune receptor known as CD27. Under normal circumstances, CD27 is switched on during infections when it binds to its natural ligand. However, cancer cells typically fail to provide this signal, leaving T cells only weakly activated and less effective at eliminating tumours.

To overcome this limitation, the team engineered a new class of antibodies designed to cluster CD27 receptors more efficiently. Unlike conventional Y-shaped antibodies, which have two binding arms, the newly developed antibodies feature four prongs. This multivalent structure allows them to engage more CD27 receptors simultaneously and bring them together into tightly packed clusters.

Crucially, the antibodies also recruit a second immune cell through interaction with a receptor known as FcγRIIB. This forced proximity amplifies the activation signal in a way that closely mimics how CD27 is naturally triggered during immune responses to infection, resulting in a much stronger instruction for T cells to attack cancer.

Professor Aymen Al‑Shamkhani, who led the study at the University of Southampton, said the work builds on long-standing biological insights but required significant innovation to translate into a therapeutic strategy. While antibodies are well-established and highly reliable drug platforms, their standard formats were not sufficient to fully activate CD27 signalling, prompting the team to design a more potent molecular architecture.

Laboratory studies using mouse models and human immune cells showed that the engineered antibodies were markedly more effective at activating CD8⁺ T cells, often described as the immune system’s elite cancer-fighting force. Compared with traditional antibodies, the four-pronged design generated stronger and more sustained anti-tumour immune responses.

By demonstrating how CD27 can be more effectively targeted, the study offers a framework for developing next-generation immunotherapies aimed at cancers that currently respond poorly to existing treatments. The researchers believe the approach could be adapted to enhance other immune pathways that rely on receptor clustering for full activation.

The work was supported by Cancer Research UK and underscores the Centre for Cancer Immunology’s role in advancing novel strategies to harness the immune system against cancer.

Harnessing Multivalency and FcγRIIB Engagement to Augment Anti-CD27 Immunotherapy is published in Nature Communications and is available online.

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SOURCE: University of Southampton