Making mother nature work for the benefit of human health

T-Cells and B-cells are the troops of the human immune system, and antibodies are the ammunition they expend to kill invaders.

But sometimes they need a little help to know who and when to attack. That’s where Ilya Trakht comes in. The Russian-born immunologist and biochemist has developed a number of groundbreaking techniques in his laboratory aimed at tackling such intractable problems as cancer, cocaine addiction, hepatitis C and malaria. 

“My research is heavily practice oriented,” he says. “We like to go from bench to bedside.”

In the case of cancer, the immune system is famously reluctant to attack tumors, because they consist of the body’s own cells, and immune responses are geared toward detecting and dispatching foreign substances.

“Cancer is a situation where we would appreciate an autoimmune system,” says Trakht. “The question I ask is whether we can somehow educate immune system to attack cancer cells. Can we recruit the immune system to target tumors?”

The answer is ‘yes.’ It turns out the immune system is not completely neutral towards pathological tumors -- rare  B-cells actually recognize tumors as a threat and will create a tiny number of antibodies in response to them. But the amount of antibodies these B-cells produce is far too little to have a significant impact--until Trakht and his team gets their hands on them. 

He’s developed a technique to extract the B-cells from the human body and render them immortal in a test tube so they can produce antibodies indefinitely. Then he watches them divide and multiply, harvests large amounts of the antibodies they create, and injects those antibodies back into the human body to attack the cancer.

To render the B-cells immortal, Trakht modified a technique that scientists have been using since the 1970s to create monoclonal antibodies. “Hybridoma technology” fuses antibody producing B-cells that are mortal with cancer B-cells that are immortal and can grow in cell culture indefinitely. The resulting hybrid has both attributes – immortality, and the ability to produce antibodies. 

The existing technology, however, relied on the cancer B-cells of a mouse, and therefore produces mouse antibodies. Upon injection in humans such antibodies would evoke an immune reaction and cause the human immune system to reject the hybrid’s antibodies before they could attack the tumor. Trakht and his lab developed a new cell line they call Human Fusion Partner (MFP-2), which is of human origin and can produce antibodies the body will accept.

“By taking these B-cells out and producing huge quantities of antibodies outside the human body (in vitro) and putting them back in with simple injection, we can tip the balance back in favor of human patient,” Trakht says.

Trakht’s new cell line, MFP-2, potentially has a wide array of other usages. Some infectious diseases, Trakht notes, develop so fast that the body doesn’t have enough time to build up a defense. His MFP-2 “platform technology” could be used to quickly create large populations of antibodies to fight off normally lethal diseases like West Nile Virus, Ebola, Rift Valley Fever, and many others.

“Once a virus enters the body, it starts spreading very fast and there is no time for an immune response,” He says. “But if you have on the shelf antibodies against virus, you can inject them into a patient and we can give the patient time to develop defense against infection.”

Trakht’s lab has a number of other projects that could have just as profound an impact. He’s hoping to begin clinical trials in 2011 on a vaccine that can render a person resistant to the effects of cocaine. He’s already shown that injections of his ant-cocaine vaccine in mice create an antibody that will prevent the cocaine “high” while also protecting against overdose.

Cocaine works because it’s a tiny molecule, small enough to evade the detection of the immune system, penetrate the blood-brain barrier and get into neurons. Trakht’s solution is to bind the cocaine to a much larger protein in vitro, then inject the compound back into the body. The protein-cocaine combinant is large enough to evoke an immune response – and once the body recognizes the miniscule cocaine molecule as an alien, it reverses its natural inclination to ignore tiny molecules and creates antibodies that will roam the bloodstream and bind to all the cocaine molecules that subsequently enter the bloodstream.

Though psychiatrists in Texas tried a similar method several years back to create a cocaine vaccine, it evoked a weak immune reaction, and only about 50 percent of patients responded to the vaccine, Trakht says. Because of the structure of Trakht’s compound—which consists of self protein and fuses the cocaine molecule directly to the surface of this protein—Trakht’s vaccine is far more effective.

“We vaccinated mice and got a 100 percent response,” he says. “Then we took the vaccinated mice, and administered enough cocaine to cause an overdose. Ten out of the 10 mice in the control group died. Not a single vaccinated mouse died.” 

Trakht is also working on a malaria vaccine. And he’s developed another innovative laboratory technique he calls “fusion and bombardment” to do it. Using a slide and centrifuge, he’s pioneered a way to fuse malaria with dendritic cells in-vitro and then inject the product into mice, which he’s shown can mobilize the body’s T-cells and invoke an effective immune response against the disease. 

Trakht has also modified the techniques he used to render B-cells immortal to create a sturdy liver cell line that will survive in the Petri dish and facilitate research on Hepatitis C that has been impossible up until now because of the fragility of hepatocyte cells. He had emulated the classic hybridoma technology to fuse immortal liver cells with mortal Hepatitis C-infected cells. Such hybrid which he calls “Hepridoma” renders the continuous production and secretion of Hepatitis C virus making it available for in vitro studies.

To view technologies from Dr. Trakht's lab, please click here