Gene Therapy for Pulmonary Diseases: Summary

In a similar study,29 the local or systemic gene transfer of IFN-7 significantly inhibited allergen-induced airway hyperresponsiveness. Another potential area for gene therapy might be in patients with steroid-resistant asthma. A study30 has shown that the transfer of the glucocorticoid receptor gene in vitro mediated the inhibition of nuclear factor-кВ activities even in absence of exogenous corticosteroids, and the authors suggested that this approach could restore corticosteroid sensitivity in patients.
This is a newer area of development with gene-based vaccines and immunotherapy of lung cancers. Here, access to the tumor is limited, and the intent is to stimulate the host immune response against unknown antigenic epitopes expressed by cancer cells in an effort to control cell growth and metasta-ses. A nonviral vector expressing IL-12 was administered through intranasal instillation in mice to inhibit lung metastatic growth of osteosarcoma, while a granulocyte-macrophage colony-stimulating factor, gene-modified, autologous tumor cell vaccine elicited vaccine-induced immune activation in patients with advanced-stage non-small cell lung cancer. Adenovirus vectors have been used to deliver intrapulmonary IFN-P to mice bearing an orthotopic graft of bronchogenic adenocarcinoma of the lung and to deliver suicide genes (herpes simplex virus thymidine kinase) to the pleural space in patients with malignant pleural mesothelioma, eliciting some surprising clinical responses. These are examples of developments that will increase as the efficacy and specificity of gene transfer to the lung increases.
Gene therapy is a promising new treatment for patients with lung diseases. Not only are patients with single gene disorders such as CF potential candidates for gene therapy, but also those with cancer and chronic lung diseases that are characterized by an imbalance of damaging and protective mechanisms. Numerous experimental models have shown that gene therapy is not a theoretical concept but is a realistic therapeutic goal. The first clinical trials in CF patients, which started almost 15 years ago, have not met expectations, mainly because of “immature” gene transfer and vector systems. However, it is anticipated that these hurdles will be overcome in the foreseeable future with the development of new vector systems and formulations allowing penetration to the epithelium, making gene therapy a feasible therapeutic alternative in patients with lung disease.

This entry was posted in Pulmonary Function and tagged a1-antitrypsin deficiency, asthma, cystic fibrosis, genetics, lung immunology.