Gene Therapy for Lung Ca.



Gene therapy administered via bronchoalveolar lavage benefited some patients with bronchoalveolar lung cancer, Dr. David Carbone said at the annual American Cancer Society science writers seminar.

Bronchoalveolar lung carcinoma spreads along the alveoli and bronchiolar surfaces, making it nearly impossible to resect. But the unique biology of this cancer also makes it possible to administer gene therapy directly to the airways, said Dr. Carbone, director of the experimental therapeutics program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

Gene therapy for other lung cancers has been of limited benefit thus far because it is difficult to expose cells in a solid tumor to the therapeutic gene.

In this pilot study, a recombinant adenovirus was the vector for delivering the therapeutic gene, p53, which induces apoptosis in cancer cells.

The virus is suspended in liquid and poured into a lung lobe through bronchoalveolar lavage. Cancer cells lining the alveoli pick up the virus and begin expressing p53; the excess fluid is absorbed by the surrounding tissue.

To date, 16 patients with advanced and unresectable bronchoalveolar lung carcinoma have been treated on an outpatient basis using the bronchoalveolar lavage technique. The same dose level of virus was given 2 weeks apart in a single affected lobe.

After two treatment cycles, a pathologic response was evident on biopsy in two patients.

Four of nine evaluated patients had a 20% or more improvement in carbon monoxide--diffusing capacity, and 4 of 11 patients reported symptomatic relief.

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