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Drug-carrying “nanoghosts” that battle melanoma and new treatments for malignant mesothelioma will be the focus of the first joint research projects led by ��ɫtv Langone Medical Center and the Technion-Israel Institute of Technology under a groundbreaking research initiative supported by noted philanthropists and ��ɫtv Langone Trustees Laura and Isaac Perlmutter.

��ɫtv Langone’s Perlmutter Cancer Center—which the Perlmutters named in 2014 with a separate gift of more than $50 million—and the Technion established the new partnership last year to advance global collaboration in cancer research and therapeutics. The joint program is positioned to attract additional, world-class support from institutions and individuals dedicated to eradicating cancer through focused and efficient research.

The first $3 million of the Perlmutters’ $9 million donation to the two institutions is earmarked to finance six joint research projects. Co-investigators on each project will receive a 2-year, $500,000 grant—$250,000 for each site. The remaining $6 million is designated to establish a state-of-the-art research facility on the Technion campus in Israel to support these and other research projects, primarily in the emerging field of cancer metabolomics, the systematic study of the unique chemical fingerprints that cellular processes leave behind. These processes are both affected by, and can influence, a variety of human diseases, including cancer.

Examining a Novel Approach to Treat Metastatic Melanoma

In the first joint collaboration, ��ɫtv Langone and Technion researchers will test the ability of a nanotechnology based on stem cell “nanoghosts” to deliver to the brain a promising treatment for metastatic melanoma, skin cancer that has spread or metastasized, and is often incurable.

In earlier studies, researchers at the Technion took a stem cell, removed its contents, and then shaped a piece of the cell’s outer membrane into a vehicle to deliver treatments into the brain. The idea was to borrow the stem cell’s outer membrane ability to home in on cancer cells. As a fragment of the former stem cell’s membrane, the nanoghost encompasses particular mechanisms that slow it enough to traverse the barrier that filters blood flowing into the brain, and which keeps most drugs from entering.

The nanoghost’s cargo is a microRNA (miR), a stretch of genetic material that fine-tunes genetic messages by blocking the conversion of genes into proteins. First applied by ��ɫtv researchers to metastatic melanoma, miR-124a, in particular, blocks the expression of cancer-promoting genes. The joint team’s experiments will seek to determine the feasibility of encapsulating miR-124a in the nanoghost and will study how the vehicle reaches its target in mouse models of the disease.

“Our studies should provide important information on nanoghosts’ general value as drug and gene carriers to the brain, and create potential for new treatment approaches against brain tumors and metastases,” says Professor Marcelle Machluf, PhD, head of the Laboratory for Cancer Drug Delivery and Cell Based Technologies at the Technion, and inventor of the nanoghost with her colleagues there. “The difficulty of delivering agents to the brain represents a major impediment to improving outcomes in patients suffering from brain tumors. Our state-of-the-art nanovehicle promises safer, simpler, and more clinically relevant treatments than existing vehicles, which are comprised of polymers or synthetic vesicles that largely lack the ability to enter the brain and to target evolving and changing pathologies.”

“It is much harder to secure funding for this type of high risk, high reward research,” says , associate professor in the  at ��ɫtv Langone, a member of the Perlmutter Cancer Center, and leader of the ��ɫtv team that first identified miR-124 as a suppressor of the growth of brain metastases. “The Perlmutters’ generous gift gives us the ability to be bold.”

Like the stem cells they are based on, nanoghosts are invisible to the immune system, which means they could potentially be made from donated stem cells, expanded to large numbers in the lab, and not just from the patient’s own supply. In the future, this could enable the stockpiling of nanoghost treatments used off the shelf without fear of immune reactions to treatments based on “foreign” cells.

New Approach to Mesothelioma

The second joint project will investigate whether an enzyme called heparanase can be used to diagnose and treat mesothelioma, a rare cancer that develops in the mesothelium, the protective lining of the lungs and other internal organs of the body. Malignant pleural mesothelioma, the most common form of the disease, often occurs after exposure to asbestos and is resistant to most therapies.

Heparanase was first identified as a treatment target in 2004 by a team led by Israel Vlodavsky, PhD, one of the project’s co-investigators and professor at the Rappaport Institute at the Technion. Past studies found that people with high levels of heparanase in their tumors have lower survival rates after surgery, and that related tumors in mice respond to treatment with heparanase-inhibiting compounds.

The enzyme breaks up molecular chains of heparan sulfate, a building block of the scaffolds that give organs shape and support. Cancer cells use the enzyme to break down tissue barriers around a growing tumor, providing new pathways for the cancer to spread and for the building of blood vessels that supply tumors. In addition, breaking up extracellular matrices releases pro-growth proteins stored there to further drive disease. The joint research team has developed the novel theory that heparanase secreted by tumor cells primes local microenvironments in a “vicious” cycle where inflammation and tumor growth drive each other.

The co-investigators at ��ɫtv Langone—led by Harvey I. Pass, MD, the Stephen E. Banner Professor of Thoracic Surgery and vice chair for research in the —will use tissue samples from its thoracic oncology archives to validate Dr. Vlodavsky’s findings in hopes of eventually evaluating the treatment potential of heparanase-inhibiting compounds in mesothelioma clinical trials. Dr. Pass has been collecting tissue samples from his surgical patients since 1989, when he was head of thoracic oncology at the National Cancer Institute (NCI). The collection now houses frozen specimens from more than 350 mesothelioma patients.

“This project, supported through the generosity of the Perlmutters, enables us to collaborate with one of the world’s leading experts on the role of heparanase in cancer, and is crucial in developing new strategies,” Dr. Pass says. "We hope that these experiments can be translated into applications for ongoing funding from the NCI, and enable Phase I trials with new therapeutics that influence heparanase pathways.”
    
“Our collaboration represents the first attempt to focus on heparanase as a major risk factor in mesothelioma and a valid target for the development of heparanase-inhibiting drugs,” Dr. Vlodavsky says. “In fact, applying a potent inhibitor of the heparanase enzyme we have already demonstrated a most prominent inhibition of tumor progression in mouse models of human mesothelioma, resulting in a pronounced extension of mouse survival. This joint effort provides an opportunity to make important strides in both our fundamental understanding of mesothelioma and in translating this knowledge into therapeutics.”

About the Technion-Israel Institute of Technology

The Technion-Israel Institute of Technology is a major source of the innovation and brainpower that drives the Israeli economy, and a key to Israel’s reputation as the world’s “Start-Up Nation.” Its three Nobel Prize winners exemplify academic excellence. Technion people, ideas, and inventions make immeasurable contributions to the world including life-saving medicine, sustainable energy, computer science, water conservation, and nanotechnology. The Joan and Irwin Jacobs Technion-Cornell Institute is a vital component of Cornell Tech, and a model for graduate applied science education that is expected to transform New York City’s economy.

American Technion Society (ATS) donors provide critical support for the Technion—more than $2 billion since its inception in 1940. Based in New York City, the ATS and its network of chapters across the U.S. provide funds for scholarships, fellowships, faculty recruitment and chairs, research, buildings, laboratories, classrooms and dormitories, and more.

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