A new antibody forces drug-resistant cancer cells to self-destruct by activating a protein called Death Receptor 5 (DR5) on their surface, while leaving healthy cells alone. This matters because many cancers—including pancreatic, ovarian, and triple-negative breast cancers—stop responding to standard chemotherapy and immunotherapy. DR5 acts as a built-in kill switch on cancer cells, but existing drugs that flip that switch have failed in clinical trials due to toxicity or weak activation. The team at Fusion Antibodies and Queen’s University Belfast has already built a prototype antibody that outperforms these earlier candidates. Now they are humanising it—replacing mouse components with human ones—so the immune system does not reject it. If the preclinical tests succeed, the result will be a clinical-trial-ready antibody that could treat multiple therapy-resistant cancers with fewer side effects than chemotherapy. The antibody could be developed by the partners or licensed to a pharmaceutical company. This project does not yet test the antibody in patients; it refines and validates the molecule so that later clinical trials can proceed safely.
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**Targeting DR5: a New Cancer Treatment Strategy** Cancer cells are like rogue agents in the body that don't follow the usual rules. To tackle these dangerous cells, scientists have found a special pathway involving a protein called **Death Receptor 5 (DR5)** (Alternative names: Tumor necrosis factor receptor superfamily member 10B; TNFRSF10B; TRAIL receptor 2; TRAIL-R2; CD262), which can tell cancer cells to self-destruct. The goal of this project is to create a new type of treatment that specifically targets DR5 to trigger the death of cancer cells. This treatment uses an "agonistic antibody", which means it can activate DR5 in a way that encourages cancer cells to die, without harming healthy cells. This selective action could lead to fewer side effects compared to traditional treatments like chemotherapy. **What Makes This Project Special?** Fusion Antibodies and Queen's University Belfast (QUB) have already developed a prototype of this new antibody that stands out from other similar treatments from an MRC CAST studentship. In this project, they aim to refine and test this prototype to ensure it's safe and effective for patient use---a process known as "humanization". **The Plan:** 1\.**Design and refine the antibody** at Fusion Antibodies. 2\.**Test the antibody in preclinical studies** at QUB's Patrick G Johnston Centre for Cancer Research. 3\.**Conduct preliminary safety evaluations** to ensure the antibody is safe for human use. The end result will be a well-tested antibody ready for clinical trials. This new treatment option could either be developed further by Fusion Antibodies and QUB or licensed to a pharmaceutical company for widespread use, ultimately benefiting patients with various types of cancer.
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