There’s a war raging in Israel, with life and death consequences worldwide. There are no tanks or tunnels. The enemy is not Iran or Hamas. This war is waged in science labs, on the battlefield of the human body. The enemy: cancer.
Israeli scientists are experimenting with immunotherapy, which manipulates the immune system to destroy cancer cells.
While immunotherapy has been around for decades, new advances in the field, coupled with recent drug approvals by the U.S. Food & Drug Administration, have intensified interest, for especially late-stage cancers that resist conventional treatments. Immunotherapy drugs already are helping patients with melanoma, lung, stomach, liver and bladder cancers, as well as some blood cancers.
“Cancer immunotherapy is exciting because, as opposed to other forms of therapy, it engages the body’s own highly sensitive system for detecting cancer cells and destroying them,” said Dr. Mark Israel, executive director of the Israel Cancer Research Fund. “This area will have a major impact on cancer outcomes going forward.”
That potential is what drew Technion’s Dr. Nathan Karin to immunotherapy research. He’s studying whether the cellular mechanisms driving autoimmune diseases like Type 1 diabetes and multiple sclerosis can be utilized to create immunotherapy drugs to fight cancer.
Karin and his team are researching the interplay between two types of cells vital to the immune system: regulatory T cells and effector T cells. Regulatory T cells tame immune system responses and prevent autoimmune diseases. But by suppressing effector T cells, they impede the body’s ability to fight cancer. “We believe that if you amplify regulatory T cells you can treat autoimmune disease, and if you block their activity you can thwart cancer,” Karin said.
Karin is among dozens of researchers receiving financial support from the Israel Cancer Research Fund. For the organization, which raises money in North America to support cancer research in Israel, it’s a challenges to decide which projects to fund. ICRF received 160 grant proposals in 2017 alone. Only a fraction will receive funding.
That’s where the U.S.-based Cancer Research Institute, known as CRI, comes in. Starting next year, ICRF and CRI will be partnering to identify and fund the most promising immunotherapy research being conducted in Israel.
A joint scientific review panel including experts from the U.S. and Canada will meet every fall to evaluate research proposals on the basis of innovation, feasibility and likelihood of impact. The initiative is called The Immunotherapy Promise.
The FDA approved the first immunotherapy drug recently, but the field dates back to 1891, when William Coley, a physician and cancer researcher, observed that some cancer patients infected by Streptococcus bacteria experienced spontaneous improvement. He began injecting the bacteria into his patients, with mixed results.
Amid skepticism and the advent of radiotherapy, the treatment was nearly abandoned.
Today, however, new avenues of research are underway, and immunotherapy is among the most promising, said Jill O’Donnell-Tormey, CEO and director of scientific affairs at CRI.
“There’s still more research that needs to be done in order to realize immunotherapy’s full potential,” O’Donnell-Tormey said. “By partnering with the Israel Cancer Research Fund, which is well known among Israel’s top academic research centers, we will be able to support more lifesaving science in a country that is home to some of the world’s most talented research scientists.”
Neta Milman, a scientist at the Laboratory for Applied Cancer Research at Rambam Clinical Research Institute in Haifa, is among ICRF’s recent grantees. She is studying pancreatic ductal adenocarcinoma, tumors that contain mostly non-cancerous cells but include a group of immune cells that promote tumor growth by producing small particles that transport genetic information to cancer cells. The small particles are called exosomes.
“We’re trying to figure out what the exosomes are sending,” Milman said. One day they could be a treatment delivery system, because they can be engineered to target cancer cells, she said.
Dr. Michal Lotem, who heads the Center for Melanoma and Cancer Immunotherapy at Hadassah, received funding to support work on a checkpoint receptor called SLAMF6, found in immune cells. When activated, these receptors modulate the immune system so that there isn’t too strong a response against normal tissues. But when it comes to cancer, the goal is to inhibit these proteins, so that the immune response against cancer will be as strong as possible.
“If you target this protein effectively, it can double or triple the effect of immune cells when they attack their target, Lotem said.
Gideon Gross and his team at MIGAL-Galilee Research Institute in the northern Israeli city of Kiryat Shemona are developing immune gene therapies, a treatment where a patient’s T-cells are modified in a lab to attack cancer cells.
Gross, a pioneer in the field, together with Zelig Eshhar at the Weizmann Institute of Science created in the 1980s the first chimeric antigen receptors, cancer-fighting molecules constructed in the laboratory and inserted into T-cells. For his ICRF project, Gross hopes to improve their performance.
For Karin, known for cutting-edge research into autoimmune diseases, the fund’s backing enabled his first foray into cancer research. “ICRF’s support was the motivation for me to get into cancer immunotherapy research,” he said. “Now most of our attention in the lab is on melanoma. Without them, we wouldn’t be doing what we’re doing.”