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Inflammatory markers, including T2 cells beta common (βc) cytokines IL-3, IL5 and granulocyte-macrophage colony-stimulating factor (GM-CSF), are known to play an important role in chronic rhinosinusitis with nasal polyps (CRSwNP). CSL311, a monoclonal antibody (mAb), was developed to target human βc receptor binding site. CSL311 is human-specific so to test it in animals, a human polyp xenograft was implanted into knock-in mice which express human IL-3 and GM-CSF. Nasal polyps from 12 participants were harvested. High levels of βc cytokines were found in the polyps as compared to control tissue from sinuses. Polyps from each patient were grafted into four-to-10 mice. Intra-polyp CSL311 treatment significantly suppressed progression of grafted nasal polyp in mice after five weeks as compared with those treated with a control mAb, with effects showing from week one. The mechanism appears to be through reduction of eosinophils, neutrophils, plasma B cells and mast cells. Histology of treated polyps showed significant decrease in mucous gland number and mucus production. On a genetic level, CSL311 was shown to suppress expression of genes responsible for the inflammatory response in nasal polyp tissue. The authors recommended assessing systemic treatment with CSL311 in animals as a step towards future clinical trials. This is an interesting controlled study on a multi-effect monoclonal antibody targeting a common cytokine-binding site of the human βc receptor. While promising, there is still long way to go before we would hopefully be able to see a topical CRSwNP monoclonal antibody treatment.

Anti‐βc mAb CSL311 inhibits human nasal polyp pathophysiology in a humanized mouse xenograft model.
K Yip, N Wilson, H Pant, et al.
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Hassan Mohammed

North East Deanery, Newcastle, UK.

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