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Prof. Lea Eisenbach of the Weizmann Institute’s Immunology Department wants to persuade the body’s immune system to fight cancer. The field of cancer immunotherapy – making use of the immune system’s weapons against malignancy – was selected the "Breakthrough of the Year" for 2013 by Science magazine. But much research is still needed to make these therapies safer and more effective.
The idea for immune-based therapy arose from the fact that the immune system constantly clears away cells that have become cancerous or are on their way to turn malignant. But obviously, since many people do get the disease, some cancer cells manage to evade the immune system’s defenses. Eisenbach is devising several strategies – so far tested only in laboratory animals – to outwit those cancer cells, enabling the immune system to seek out and destroy them.
As a first step, she and her team identified a number of proteins and protein fragments that in cancerous tumors are mutated or present in higher than normal amounts. In experiments in mice, these protein fragments were used as a vaccine that eliminated lung cancer metastases and other tumors, including those produced in mice by various human cancer cells.
To further develop anti-cancer vaccines, Eisenbach’s team and their collaborators in the MIGAL Research Institute in Kiryat Shmona are teaching the immune system to detect evasive cancers with the help of dendritic cells, the system’s sentinels that normally alert it to the presence of viruses, bacteria and other dangers. The scientists achieve this goal by outfitting dendritic cells with the above-mentioned protein fragments fused with additional molecules that trigger an immune response. By making use of RNA molecules, which convey genetic information but are easier to manipulate than the genes themselves, they have been able to engineer several of the tumor’s genetic features into a dendritic cell, thus increasing the chance that the tumor will be detected.
The engineered dendritic cells can then serve as a vaccine: They migrate to lymph nodes, where they activate the immune system against cancer, priming it into attacking a tumor it previously did not recognize. In a recent review in the Annals of the New York Academy of Sciences, the scientists noted that studies in mice point to the potential efficacy of this approach against metastases of melanoma, particularly those that move to the lungs.
But the best way to fight cancer is to prevent it. In another project, Eisenbach’s team is focusing on a family of genes called IFITM that encode a group of interferon-activated genes believed to play a protective role against inflammation of the colon, which, in turn, may contribute to cancer. In a study in mice, the scientists showed that in the absence of IFITM genes, the incidence of inflammation in the colon did indeed increase, and with it the risk of colon cancer. Because in humans IFITM genes can be present in different variants, it’s possible that people with certain versions that are relatively ineffective at warding off inflammation are more prone to colon cancer than those with optimally functioning IFITM genes. This research may in the future help develop markers for identifying people at increased risk of colon cancer.
In yet another avenue of research, Eisenbach has focused on a phenomenon called “split immunity” to investigate potential ways of treating glioblastoma, an extremely malignant brain tumor. In research conducted by Dr. Ilan Volovitz, then a student in Eisenbach’s lab, with departmental colleague Prof. Irun Cohen, she and her team found that glioblastoma cells produced highly malignant tumors in rats when implanted into their brains, but these same cells were eliminated by the immune system when implanted in the backs of the rats. When the glioblastoma cells were implanted in the brains of rats that had already rejected tumors in their backs, however, no tumors formed there: Apparently, the previous injections in the back had somehow primed immune T cells to effectively fight the brain tumors.
As reported in the Journal of Immunology, the researchers further discovered that existing tumors in the brains of rats could be effectively treated by injecting the animals with T cells drawn from other rats that had cleared these tumors in their backs. Dr. Volovitz and Prof. Zvi Ram, both of the Tel Aviv Sourasky Medical Center, are now continuing to develop this approach.
Prof. Lea Eisenbach's research is supported by the Jeanne and Joseph Nissim Foundation for Life Sciences Research; the Victor Pastor Fund for Cellular Disease Research; the Pearl Welinsky Merlo Foundation Scientific Progress Research Fund; the Lewis Family Charitable Trust; and the estate of John Hunter. Prof. Eisenbach is the incumbent of the Georg F. Duckwitz Professorial Chair of Cancer Research.
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