Isolation of an IL-13-dependent subclone of the B9 cell line useful for the estimation of human IL-13 bioactivity

Bouteiller, Christine Labit-Le; Astruc, R.; Minty, Adrian; Ferrara, P; Lupker, Jan H.

doi:10.1016/0022-1759(94)00323-o

Cited by 9 publications

(1 citation statement)

References 17 publications

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“…This was achieved by the targeted replacement of the mouse gene with the human gene, from start to stop codon, retaining a mouse promoter and pA tail. This was considered a rational approach as human IL‐13 can drive mouse hybridoma B9 cell proliferation in a similar fashion to mouse IL‐13 (Bouteiller et al ., 1995). In addition human IL‐13 has been shown to mimic the effects of mouse IL‐13 in the mouse lung driving eosinophilia and AHR (Blanchard et al ., 2005).…”

Section: Discussionmentioning

confidence: 99%

Preclinical development of CAT‐354, an IL‐13 neutralizing antibody, for the treatment of severe uncontrolled asthma

May¹,

Monk

Cohen³

et al. 2012

British J Pharmacology

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BACKGROUND AND PURPOSEIL-13 is a pleiotropic Th2 cytokine considered likely to play a pivotal role in asthma. Here we describe the preclinical in vitro and in vivo characterization of CAT-354, an IL-13-neutralizing IgG4 monoclonal antibody (mAb), currently in clinical development.EXPERIMENTAL APPROACHIn vitro the potency, specificity and species selectivity of CAT-354 was assayed in TF-1 cells, human umbilical vein endothelial cells and HDLM-2 cells. The ability of CAT-354 to modulate disease-relevant mechanisms was tested in human cells measuring bronchial smooth muscle calcium flux induced by histamine, eotaxin generation by normal lung fibroblasts, CD23 upregulation in peripheral blood mononuclear cells and IgE production by B cells. In vivo CAT-354 was tested on human IL-13-induced air pouch inflammation in mice, ovalbumin-sensitization and challenge in IL-13 humanized mice and antigen challenge in cynomolgus monkeys.KEY RESULTSCAT-354 has a 165 pM affinity for human IL-13 and functionally neutralized human, human variant associated with asthma and atopy (R130Q) and cynomolgus monkey, but not mouse, IL-13. CAT-354 did not neutralize human IL-4. In vitro CAT-354 functionally inhibited IL-13-induced eotaxin production, an analogue of smooth muscle airways hyperresponsiveness, CD23 upregulation and IgE production. In vivo in humanized mouse and cynomolgus monkey antigen challenge models CAT-354 inhibited airways hyperresponsiveness and bronchoalveolar lavage eosinophilia.CONCLUSIONS AND IMPLICATIONSCAT-354 is a potent and selective IL-13-neutralizing IgG4 mAb. The preclinical data presented here support the trialling of this mAb in patients with moderate to severe uncontrolled asthma.

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Section: Discussionmentioning

confidence: 99%