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Bert O'Malley
Bert O'Malley began Phase 1 gene therapy trials last winter.


he only thing that’s even vaguely good about head and neck tumors, according to otolaryngologist/oncologist Bert W. O’Malley Jr., M.D., is their accessibility. “Without too much trouble,” he says, “you can reach the tumors with a needle. That gives them great possibility as a target for gene therapy.”

And O’Malley has used this easy access to advantage. Last winter he began Phase I gene therapy trials for patients with advanced head and neck cancers—tumors notoriously resistant to treatment. Moreover, the gene tech company that’s teamed with him has added a twist to the therapy that gives it potential for a far greater than normal attack on the tumors.

The therapy operates by generating small pools of interleukin-2 (IL-2) in the vicinity of the tumor cells. IL-2, among other things, prods the immune system to produce tumor-attacking white blood cells. A few years back, researchers tried a whole-body infusion of the protein, but systemic IL-2 proved too toxic. Local IL-2, however, mimics a natural release, bringing hope for tumor death without harm to patients.

With a syringe, O’Malley injects the tumors with IL-2 genes carried on plasmids, the circular bits of DNA commonly known as gene therapy’s workhorses. But the trick to what he’s doing, he says, involves getting the plasmids into tumor cells. He injects plasmids suspended in a lipid solution. “Lipids are a craze right now,” says O’Malley. “They’re hot because they bind with the DNA plasmids and then slip through cell membranes, delivering the therapeutic gene.” And what makes the Hopkins trials so special, he adds, is that the precise combination of lipid and plasmid they use triggers an unexpected outpouring of other interleukin-like molecules, each with its own powerful antitumor effect. “Lots of people are trying IL-2 gene therapy,” says O’Malley, “but this is something unusual.”

So far, O’Malley has injected 10 patients, either prior to standard surgery/radiation or afterward. Patients with tumors too advanced for surgery have gotten the genes as well. All remain free from notable side effects, and tests show their new IL-2 genes are turned on. The next step, testing the safety of multiple and higher doses while looking for signs of efficacy, begins this summer. “It’s got a chance,” says O’Malley. “The principles are nice, the method makes sense, so we hope it’ll be effective clinically.”

-- MC