With all the uncertainty of COVID-19, we hope you are safe and in good health. Ozgene is still here to meet your research needs.

Preclinical development of CAT-354, an IL-13-neutralising antibody, for the treatment of severe uncontrolled asthma.

 Back to publications

2011

Br J Pharmacol 2011 Sep 6. doi: 10.1111/j.1476-5381.2011.01659.x. [Epub ahead of print]

Preclinical development of CAT-354, an IL-13-neutralising antibody, for the treatment of severe uncontrolled asthma.

May, R;Monk, P;Cohen, E;Manuel, D;Dempsey, F;Davis, N;Dodd, A;Corkill, D;Woods, J;Joberty-Candotti, C;Conroy, L;Koentgen, F;Martin, E;Wilson, R;Brennan, N;Powell, J;Anderson, I.

MedImmune, Abington, Cambridge, UK.

Service type: Humanized mice

Abstract

Background and purpose:  IL-13 is a pleiotropic Th2 cytokine considered likely to play a pivotal role in asthma. This paper describes the preclinical in vitro and in vivo characterisation of CAT-354, an IL-13-neutralising IgG4 mAb, which is currently in clinical development. Experimental approach:  In vitro the potency, specificity, and species selectivity of CAT-354 was assessed in TF-1, HUVEC, and HDLM2 cell-based assays. The ability of CAT-354 to modulate disease relevant mechanisms was tested in bronchial smooth muscle calcium flux, NHLF eotaxin generation, PBMC CD23 upregulation, and B cell IgE production assay systems. In vivo CAT-354 was tested in huIL-13-induced air pouch inflammation, IL-13 humanised mouse ovalbumin-sensitisation and challenge, and cynomolgus monkey antigen challenge models. Key results:  CAT-354 has a 165pM affinity for human IL-13 and functionally neutralises human, human variant associated with asthma and atopy (Q130R), and cynomolgus monkey, but not mouse IL-13. CAT-354 is selective for human IL-13 and does not neutralise IL-4. In vitro CAT-354 functionally inhibits IL-13-induced eotaxin production, an analogue of smooth muscle AHR, CD23 upregulation, and IgE production. In vivo, in humanised mouse and cynomolgus antigen challenge models, CAT-354 inhibits antigen-challenge induced AHR and BAL eosinophilia. Conclusions and implications:  CAT-354 is a potent and selective IL-13-neutralising IgG4 mAb. The preclinical data presented here support the trialling of this mAb in patients with moderate-severe uncontrolled asthma.

View Publication