New Research From Israel

T o Ofer Mandelboim, cells infected with viruses and cancer are “enemies” that he must destroy. And a new grant will help him boost his fight against these invaders. “We are surrounded by enemies,” said Mandelboim, a professor of molecular immunology at Hebrew University – Hadassah Medical School’s Lautenberg Center for General and Tumor Immunology. “The question is, why do we live for such a long time? What enables this living is our immune system?”

To battle these aggressive cells, Mandelboim focuses on the immune system, which has two sections in every person, Mandelboim explained. The first, called the innate immune system, disperses its fighters to attack hazardous cells immediately, within the first week or two after infection. The second, called the adaptive immune system, functions through memory and adapts to future situations based on previous events.

“[The immune system] remembers you were infected once, and the second time this system will operate much stronger,” Mandelboim said. “But it takes time.”

His research focuses on the former — the innate immune system — and a particular group of cells called “natural killer cells” within this system.

“Their job under normal conditions is to kill virus-infected cells and cancer cells,” he said. “We are studying how these anchor cells — the natural killer cells — can recognize the tumor cells, and what is the mechanism [that cancer cells use] to avoid the natural kill cells.”

If scientists can uncover the mechanisms used by tumor cells to avoid the natural killer cell attacks, they could potentially develop means to block this pathway, he explained.

“What is even more amazing is that, during pregnancy, these [natural killer cells] help the baby to develop,” Mandelboim added, explaining that the cells travel though blood between the mother and child in order to help the baby grow.

Mandelboim’s laboratory recently founded a startup company with a partner research group at Ben-Gurion University in Beersheva. While his lab seems to be doing well, Mandelboim stresses the need to significantly improve the government’s focus and funding to scientific education and research.

“There is no money [in Israel] for research,” he said.

Mandelboim’s professorship is funded by the Israel Cancer Research Fund; the seven-year grant is for $50,000 per year.

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In a world where both diseases and treatments are becoming increasingly unique in their structures and symptoms, one Israeli pharmaceutical company is targeting a process that is integral to nearly every illness — apoptosis, or cellular death.

“Apoptosis is associated with almost every medical disorder,” said Yoram Ashery, CEO of Aposense, a clinical stage molecular imaging and drug development company that completed its Initial Public Offering on the Tel Aviv Stock Exchange in June.

Under the leadership of Ashery and a team of scientists, Aposense is currently in stage two in clinical trials of a versatile molecular imaging technique that would allow scientists to produce detailed images of apoptosis; such imaging would enable them to come closer to understanding the different mechanisms that cause cell death in diseases such as cancer. Apoptosis has been a target of researchers ever since molecular imaging capabilities emerged, and several companies worldwide have been working on finding a viable imaging mechanism for cellular apoptosis, according to Ashery.

“The field of molecular imaging is about a decade old,” he said. “Specifically with apoptosis, we are the only ones to have succeeded so far. We are not the first to try to shoot at this target.”

For Aposense, according to Ashery, the purpose of developing this technology right now is two-fold. First, its research will allow scientists to get a closer analysis at how cell death occurs through the molecular imaging process. Second, its technology can serve a therapeutic purpose –using the same platform, Ashery says, scientists hope to be able to inject the cancer cells precisely with medicines. To accomplish this, Aposense is currently working with Israeli pharmaceutical giant Teva to “reach dying cells of very high specificity” through the imaging technology.

“The idea is we can deliver something to that cell and that something can be an imaging tracer or a therapeutic compound, which will then do the therapeutic work on that cell,” he said.

Trials are taking place in the U.S. and Israel and have already had success on human subjects. Ashery expects that they will enter stage three — the final phase in clinical trials according to the FDA — by 2012. Should FDA approval happen, he says the company’s technology could have applications for a wide breadth of illnesses.

“This opportunity is rare,” Ashery said. “In the biotech world, technologies are becoming more and more disease-specific. This is a very cross-disease technology — it’s applicable to a lot of diseases, to most diseases I would say.”

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Rotem Karni, a senior lecturer of biochemistry and molecular biology also at Hadassah Medical Center, is a new Israel Cancer Research Fund grant recipient who is working on battling cancer in its earliest stages. His grant is aimed at up-and-coming scientists early in their careers.

“This specific project of the research is to study the evolvement of specific splicing factors in metastatic breast cancer,” Karni said. “We have very striking findings that inhibiting this factor can inhibit the metastasis of these cells.”

“If we can find a way to inhibit it in patients we can actually help to develop therapy against metastatic stage, which is the deadliest stage of any cancer,” Karni added.

Karni intends to use his newly rewarded grant money to help recruit students and purchase new supplies that could be integral in his research. Meanwhile, he recently met with a U.S. company potentially interested in helping develop the ways to inhibit the splicing factor.