Immunological hurdles to lung gene therapy.
Clin Exp Immunol
; 132(1): 1-8, 2003 Apr.
Article
in En
| MEDLINE
| ID: mdl-12653829
ABSTRACT
Gene delivery has the potential to offer effective treatment to patients with life-threatening lung diseases such as cystic fibrosis, alpha1-antitrypsin deficiency and lung cancer. Phase I/II clinical trials have shown that, in principle, gene transfer to the lung is feasible and safe. However, gene expression from both viral and non-viral gene delivery systems has been inefficient. In addition to extra- and intracellular barriers, the host innate and acquired immune system represents a major barrier to successful gene transfer to the lung. Results from studies in experimental animals and clinical trials have shown that inflammatory, antibody and T cell responses can limit transgene expression duration and readministration of the gene transfer vector. We will review here how the development of pharmacological and/or immunological agents can modulate the host immune system and the limitations of these strategies. A better understanding of the immunological barriers which exist in the lung might allow for a more sustained expression of the transgene and importantly help overcome the problem of readministration of viral vectors.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Therapy
/
Lung
/
Lung Diseases
Limits:
Humans
Language:
En
Journal:
Clin Exp Immunol
Year:
2003
Document type:
Article
Affiliation country:
Reino Unido