Gene Therapy: A Promising Role in Otolaryngology

Gene therapy has had a tumultuous past, and this legacy has created hesitation to pursue gene therapy in the present. There has been almost a dearth of gene therapy research despite its potential. – -Gary B. Clayman, DMD, MD

A 21st Century Renaissance

With this tumult serving as both a backdrop and a caution, gene therapy investigators in the 21st century agree that the field is enjoying a renaissance. They have learned from their colleagues’ errors, and the current thinking in gene therapy research is that new enthusiasm has surfaced for a field that is still very much alive and rapidly growing, Dr. O’Malley said. The field is growing at as rapid a pace as ever, but with more appropriate expectations than in the past.

He distinguished between treatment of genetically based diseases through correcting the genetic abnormality in all or a majority of cells within a tissue or body organ and the specific use of genes for therapeutic purposes. An example of the first case would be pancreatic transplant for type 1 diabetes, because the patient needs a pancreas with a completely different genetic structure. Solving the genetic issue in each cell is much harder than using a gene that, when introduced into the body or an organ, will produce an agent that will alter the disease process without correcting the actual defect within the DNA, he said.

We can use therapeutic genes to correct the process in many different illnesses or diseases within our specialty of otolaryngology, said Dr. O’Malley. In head and neck cancer, for example, investigators are developing genes that halt tumor growth or kill the tumor directly either by injecting the gene into the tumor or through intravenous infusion of genes with targeting mechanisms that are taken up into the tumor cells.

One gene-based treatment for head and neck tumors has advanced into two ongoing Phase III trials, an adenovirus vector inserted with p53 (Advexin). This therapy is being developed for treating clinically advanced, recurrent squamous cell carcinoma of the neck, Dr. Clayman said. These are the only phase III studies regarding gene therapy in head and neck surgery that I know of, he said.

The research on p53 in the adenovirus vector began in 1998, Dr. Clayman said, noting that the resultant Phase I and II studies showed sufficient promise that he and other investigators wanted to study the treatment in a large clinical trial. Although we saw no dose-limiting toxicities, this therapy is restricted to intratumoral injections, he said. We’re not yet able to target the lesion by systemic injection.