Science in Mind

Russian medical therapy may lead to new way to boost vaccines’ potency

Mark Poznansky, right, and Satoshi Kashiwagi, left, with the laser they've used to move forward an insight first made a decade ago by a Mass. General team sent to Russia.
Mark Poznansky, right, and Satoshi Kashiwagi, left, with the laser they've used to move forward an insight first made a decade ago by a Mass. General team sent to Russia.Credit: Michele McDonald for the Boston Globe

The Cold War had been over for well over a decade when a Boston physician arrived in St. Petersburg to visit a Russian military medical clinic, as part of a US State Department effort to steer former Soviet scientists away from biological weapons and toward peaceful research that could be commercialized.

He found doctors using a powerful, potentially explosive laser designed for military applications to treat patients with advanced kidney cancer. They shone the laser light onto patients’ backs, sometimes raising small welts, and then injected them with vaccines prepared from their own tumor cells.

It sounds sinister, even barbaric. But the more Dr. Jeffrey Gelfand, a physician at Massachusetts General Hospital, learned, the more impressed he became.

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“I saw patients with renal carcinoma who I thought were doing astoundingly well compared to what was happening in the States,” Gelfand said. Patients with advanced cancer appeared to be “surviving for really, a very prolonged period—years,” he said.

After Gelfand’s return, a startup, Boston BioCom, was set up to commercialize the technology, which the Russian doctors also used to strengthen the body’s natural immune responses to an array of vaccines. And colleagues at Mass. General’s Vaccine and Immunotherapy Center began doing basic animal studies to verify and probe the science behind the powerful effects Gelfand had seen. On Wednesday, the team reported in the journal PLOS ONE that a different kind of laser increased the potency of a flu vaccine in mice.

More studies will need to be done to see whether a laser treatment could make vaccines work better in people, but outside researchers said the results were promising. And the idea, which Gelfand and colleagues admit was viewed skeptically at first, has been given a major vote of confidence—a four-year, $1.6 million grant from the National Institutes of Health to understand the biological reasons behind the effect.

“It’s to me very encouraging that people are thinking of things that haven’t been tried yet and showing they can work,” said Dr. Pritish Tosh, an infectious disease physician and vaccine researcher at the Mayo Clinic. “This is innovative and intriguing.”

The finding, which researchers hope could lead to human clinical trials soon, is the end result of an effort that took Gelfand and his team across the former Soviet Union to review more than 200 technologies in the mid-2000s. They traveled to an institute in Siberia where the building housing a smallpox laboratory was guarded by a .50-caliber machine gun, passed guards who joked, “you’re the seventh American to leave this building alive,” and visited poorly heated laboratories where determined scientists continued their research despite drastic funding cuts.

Gelfand led a team of seven who conducted a kind of scientific American Idol, in which researchers seeking funding would pitch their work. The team was specifically interested in biomedical research that could be validated and commercialized. They passed on many projects, including proposals to make artificial caviar and to immunize chickens against influenza by having them walk through a mist of weakened virus.

The American team did more than just hand out money—they started ongoing partnerships with Russian researchers, introduced them to investors, and helped them write business plans.

They were confident that there was something to the laser treatment, but they had to go back to basics. The data weren’t sufficient to start clinical trials in the United States, so they needed to do the rigorous animal studies to replicate the effect. And they wanted to see whether it would be possible to replace the large, powerful military laser used by the Russians with a portable, hand-held device.

At Mass. General, Dr. Satoshi Kashiwagi and Dr. Mark Poznansky led a team that spent nearly a year trying out different lasers to determine a safe dosage in mice.

They were encouraged when they found that an invisible, near-infrared laser administered for a minute enhanced an immune response to flu vaccine in mice. The researchers did detailed studies of the response, and although they do not fully understand the mechanism at work, they believe that the laser causes skin cells to release chemical signals that draw immune system cells to the area.

As a final test, the Mass. General researchers administered a flu vaccine into the skin of the mice after the laser treatment and then exposed them to a high dose of flu virus. Half the mice given a laser treatment in addition to the vaccine survived, whereas only a quarter of the mice given the vaccine alone lived.

The mice treated with the laser did nearly as well as those that received the vaccine with a chemical adjuvant, which are often combined with vaccines to boost their potency. Chemical adjuvants, however, may cause side effects. The 2009 H1N1 vaccine that was given with an adjuvant in Europe was linked to increased cases of narcolepsy.

The researchers have done a small safety trial of the laser in people, and hope that they can test it in clinical trials soon. They are thinking broadly: perhaps laser treatment could increase the effectiveness of vaccines in populations for whom they don’t work very well, such as elderly people. Perhaps vaccines given in multiple doses, such as the hepatitis B or HPV vaccine, could be reduced to fewer shots by adding a laser treatment, which might increase use of such vaccines.

Dr. Sergey Onikienko, a professor in the department of military therapy at the St. Petersburg Military Medical Academy, led the work that inspired the new study. He began researching medical applications of lasers in the late 1970s.

First, he said, he found that lasers could be used to spur wound healing in animals, and over the years his research expanded into more and more applications—and into human patients.

Through an interpreter, Onikienko said he felt proud that his work had been validated and extended in the new study.

“I think as a scientist, looking back, empirical data are great,” Onikienko said. “But clearly this work needed fundamental understanding of what was going on.”

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