Antibody Response to Aerosolized Transgenic Human Alpha<sub>1</sub>-Antitrypsin

Lt, Spencer; Je, Humphries; Ml, Brantly

doi:10.1056/nejm200505123521923

Cited by 41 publications

(26 citation statements)

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“…A pilot study in CF patients using recombinant a 1 -AT derived from transgenic sheep showed no allergic effects up to doses of 500 mg recombinant a 1 -AT?day -1 [133]. Nevertheless, use of recombinant a 1 -AT may have the problem of antibody responses to traces of inhaled nonhuman proteins and may lead to anaphylactic reactions [134]. Tables 3 and 4 summarise published studies using BAL (table 3) and sputum (table 4) to assess the effect of inhaled a 1 -AT in patients with CF lung disease.…”

Section: Inhibition Of Free Elastase By Inhaled a 1 -At Inmentioning

confidence: 99%

Inhibition of airway proteases in cystic fibrosis lung disease

Griese¹,

Kappler²,

Gaggar³

et al. 2008

European Respiratory Journal

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Progressive lung disease determines the morbidity and mortality of cystic fibrosis (CF) patients.CF lung disease is characterised by endobronchial inflammation sustained by bacterial infections and an ongoing accumulation of airway neutrophils. Activated or necrotic neutrophils liberate proteases that cause damage to structural, cellular and soluble components of the pulmonary microenvironment.Among various proteases released by airway cells, elastase is considered to play the major role in CF lung disease. Based on this concept, several therapeutic approaches have been developed to inhibit free elastolytic activity, including small synthetic chemical compounds, semi-synthetic inhibitors and natural inhibitors of free elastase.The present review summarises and discusses the pathophysiological rationales, methodological requirements and clinical implications of inhibition of airway proteases in cystic fibrosis lung disease.

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Section: Inhibition Of Free Elastase By Inhaled a 1 -At Inmentioning

confidence: 99%

Inhibition of airway proteases in cystic fibrosis lung disease

Griese¹,

Kappler²,

Gaggar³

et al. 2008

European Respiratory Journal

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“…Particle sizes ranging from 1 to 5 μm appear to be optimal for reproducible drug delivery to the airways [118,119]. The agent should be sterile and nonpyrogenic as allergic reactions to impure recombinant or plasma-purified preparations may occur [120]. To aid in patient compliance it should be reasonably palatable.…”

Section: Delivering An Agent To the Lungmentioning

confidence: 99%

Targeting neutrophil elastase in cystic fibrosis

Kelly

Greene

McElvaney

2008

Expert Opinion on Therapeutic Targets

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“…Transgenic production of human A1AT has been achieved in mice, rats, rabbits, sheep and goats [116][117][118][119][120]. Spencer et al raised concern regarding antibody responses seen in some recipients due to impurities in the aerosolized human A1AT produced from the milk of transgenic sheep [121]. The potential for immune-mediated responses to transgenic proteins has currently halted the clinical development of these products.…”

Section: Recombinant/transgenic Augmentationmentioning

confidence: 99%