This article first appeared in the St. Louis Beacon, March 15, 2012 - Everybody knows science can’t cure the common cold but Dr. David Curiel thinks that with a little research, he’s hoping the common cold can cure cancer.
“That’s the ironic spin on the story,” said Curiel, director of Washington University’s Biologic Therapeutics Center (BTC). “Folks thought that nanotechnology gave us the possibility of building this holy grail agent. It’s turning out that a biological agent that we’ve studied for years and years may actually be the entity that embodies all the capacities that we need.”
That holy grail has come in the form of adenovirus, one of the little bugs that cause cold symptoms in humans. Curiel, along with other scientists at Washington University and elsewhere, are working to reengineer the microscopic packet of DNA so it will gain a taste for tumors where it can deliver a potent payload of radioactive metals and therapeutic genes.
The research, funded by a grant from the National Institutes of Health, has been going on since late last year. It’s been largely the result of a blend of older medical ideas with newer insights about the boundaries of microscopic bio-warfare and the potential of recruiting certain viruses to be on our side in the battle against one of humanity’s most widespread health threats.
For Curiel, this sort of cutting edge biotech work is just what the doctor ordered. A former head of the University of Alabama’s gene therapy program, the Atlanta native now helms the BTC, an ambitious initiative created by the university last year to boost its presence in translational research, a “bench-to-bedside” field that works to give scientists the tools to turn raw data into real world treatments.
An unexpected crash of ideas
Researchers had long had the idea of employing artificial nanoparticles, tiny inert bits of matter, as special purpose vehicles for targeting tumors. The hope was to use them as what are known as theranostics agents, particles that could effectively find the tumor, deliver treatment and provide a method for assessing efficacy by aiding in imaging through an MRI or CT scan. It was an idea the National Cancer Institute found deeply promising.
Surprisingly, many of the ideas that underpin the new research on shrinking tumors had been around for a while, just not all under the same roof. While Curiel was looking at how to target the cancer, Mike Mathis, a colleague at Louisiana State University, was exploring the imaging aspect and Buck Rogers, a Washington University researcher was working with viruses.
“It’s like that old commercial where the two kids are on bikes and one has chocolate and one has peanut butter and they crash,” Curiel said. “We hadn’t thought in those terms but we thought maybe instead of a nanoparticle maybe a virus can do all those things.”
The idea became more promising with recent advances in technology and the conclusion of Phase I research on viruses that target brain tumors and ovarian cancer. It was the first ever use in humans of a virus similar to that which Curiel and the others were beginning work on.
“It’s an earlier generation of what we are trying to do here. It embodied the principle of a radically altered virus in humans,” he said. “They just finished that trial the fall before last which shows you how quickly these things progress.”
He noted that viruses are already being injected directly into tumors by physicians in China. Researchers here thought it could be taken a step further with a virus that actually used the bloodstream to find the tumor on its own.
The folks with the purse strings got onboard quickly using a special “exceptional funding” procedure.
“When the NIH sees something they think is so interesting, they pull it out of the normal review process and just fund it,” Curiel said. “That’s what they did for us.”
The adenovirus turned out to be a perfect choice. Heavily researched since the 1960s, it was well-known and, with its natural resilience and plasticity, the bug proved a cooperative subject for reengineering into a tumor fighter.
But even the pluckiest virus needs an assist, one that came in this case from camels. The researchers eventually found that, when attached to the viral shell, certain camel antibodies were proving useful in enhancing the cancer-killer’s targeting abilities. They began working with a veterinary school in Boston.
“That was something we didn’t even envision when we started in the fall, but now it has given additional feasibility to our approach,” said Curiel.
So-called “monoclonal antibodies” were not a new concept. They had once been hailed as potential “magic bullets” for cancer treatment but human trials had shown there were still problems to be hashed out.
“Gene therapy has a similar story,” said Curiel. “Initially a lot of enthusiasm, disappointing trials and now the field is seeing, in the last year, spectacular cures in humans.”
Gene transfer capacity, like that seen in gene therapy, is one thing that gives the researchers’ bugs an advantage. Curiel said the virus, with its ability to drill into a cell and deliver genetic material, showed itself to have greater potential than a simple nanoparticle. Binding radioactive metals to its surface further enhanced its abilities.
Curiel said research continues on the potential viral solution to tumors. Meanwhile the BTC has scheduled a symposium on gene therapy for September.
“We have ‘bench to bed’ goals and we think this is a strongly translational project,” he said.
In the meantime, Curiel and the others involved in the project are getting their share of attention in the media. A recent story on the research in the Shreveport, La. Times newspaper was bannered on the front page under the headline “Curing cancer.”
There is, of course, a long way to go, and years of data collection remain ahead. Are such headlines overstating things a bit?
Curiel chuckles over a truism of research.
“It’s always overstatement until it’s done,” he said.