Anchor a TGF-beta trap in the tumour stroma so it cannot act everywhere
A powerful immune-suppressing signal called TGF-beta keeps immune cells out of tumours, but blocking it throughout the body causes heart and skin problems. Tethering the blocker inside the tumour could give benefit without the harm.
Systemic TGF-beta blockade, including the PD-L1-TGF-beta trap bintrafusp alfa, failed largely on a narrow therapeutic index with bleeding and cardiac toxicity. Localisation strategies — a FAP-anchored trap, a collagen-binding domain fusion, or a protease-activated masked format — restrict activity to stroma-rich tumour tissue, and masked antibody formats are already in clinical trials.
- Cold tumours and the immunosuppressive microenvironment · Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.
- Toxicity and quality of life are undervalued · Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated.
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