In a recent study published in Molecular Cancer Therapeutics, researchers at the Weizmann Institute of Science in Rechovot have paired the active ingredient of a garden parasite killer with advanced bio-technology to deliver a powerful punch against cancer.
The cancer-killing effectiveness lies in the researchers' technique of arming a cancer-targeting antibody with the destructive potential of the molecule known as allicin. Allicin is the product of an interaction between the enzyme allinase and the small chemical alliin, which occurs naturally in plants such as garlic and onion as a defense mechanism against soil fungi, bacteria and parasites.
Professor David Mirelman, Prof. Meir Wilchek, Drs. Fabian Arditti, Talia Miron and Aharon Rabinkov of the Biological Chemistry Department, and Prof. Yair Reisner of the Immunology Department, together with Prof. Berrebi of Rechovot's Kaplan Hospital, adopted an approach that fastens the enzyme allinase onto a specific antibody already in clinical use, Rituximab, designed to target and lock on to the surface of certain types of cancer cells such as lymphoma. When administered alone, Rituximab serves as a marker and docking point for the body's own immune system to kill the cancer cell. The Institute team demonstrated that cancer cells could be destroyed more efficiently by binding allinase to this antibody and triggering the production of allicin while the allinase is attached to the cancer cell.
Although other approaches use a method that directly binds anti-cancer drug molecules to an antibody, this study applied a method Prof. Mirelman refers to as "weaponizing" an antibody, so called because it affords the continuous production and delivery of cancer-killing "bullets": the allinase that is bonded to the Rituximab sits on the target cell and continuously reacts with alliin molecules that are injected at intervals, producing a steady supply of allicin to penetrate and kill the cancer.
In the war on cancer, in addition to the aforementioned "ground troops" armed with the latest weapons, there are also efforts underway to disrupt enemy communications.
In a study published recently in the Proceedings of the National Academy of Sciences (USA), a team of Weizmann Institute scientists demonstrated how the right combination might form a web that destroys the cancer cell's communication network, ultimately demobilizing the cell. Three decades of intensive cancer research led to the identification of a family of receptors, known as HER, that sit antenna-like on the outside of the cell wall and are implicated in certain types of cancer. A team of researchers under Professor Yosef Yarden, Dean of the Weizmann Institute's Feinberg Graduate School and a professor in the Institute's Biological Regulation Department, and Prof. Michael Sela, former president of the Weizmann Institute of Science and currently a professor in the Institute's Immunology Department, teamed up to create a strategy for the customization of antibodies that work independently to engage these cancer-specific receptors and shut down the attendant signaling network.
The study was carried out in cooperation with researchers from Targeted Molecular Diagnostics, Westmont, IL, USA.
Finally, in the campaign against cancer, Weizmann scientists have discovered how the enemy's undercover agents have been infiltrating the ranks.
Disease agents called retroviruses, responsible for causing AIDS and cancers such as leukemia, manage to sneak into cells with the help of special protein assemblies scattered all over their surfaces. These retrovirus surface proteins cause the membrane envelope of the virus to fuse with the membrane of the cell, spilling virus RNA into the cell to wreak damage. Now, a team of scientists at the Weizmann Institute and the Max Planck Institute for Biochemistry has obtained a close-up 3-D portrait of the large protein complex on the virus that enables its entry into the cell. Their work appeared in the Proceedings of the National Academy of Sciences in March.
Dr. Deborah Fass of the Weizmann Institute's Structural Biology Department and student Nathan Zauberman teamed up with scientists from Max Planck's Molecular Structural Biology Department in Martinsried, Germany. They saw strong evidence that the protein complex undergoes a radical change in shape and arrangement of its component parts as it attaches to cells and initiates membrane fusion. Fass was able to see how a smaller protein piece she had previously isolated and analyzed by crystallization fit into the whole, giving her further clues as to how the virus locks onto the cell membrane.
[For more 2005 reports on Israeli advances in the war against cancer, see:
1. "Israeli Study - Turmeric Prevents Colon Cancer"
2. "Israeli Scientists Develop 'Micro Missile' to Combat Cancer"
3. "Israeli Technology to Help Breast Cancer Patients"
4. "Fighting Cancer With a Tree"]
The cancer-killing effectiveness lies in the researchers' technique of arming a cancer-targeting antibody with the destructive potential of the molecule known as allicin. Allicin is the product of an interaction between the enzyme allinase and the small chemical alliin, which occurs naturally in plants such as garlic and onion as a defense mechanism against soil fungi, bacteria and parasites.
Professor David Mirelman, Prof. Meir Wilchek, Drs. Fabian Arditti, Talia Miron and Aharon Rabinkov of the Biological Chemistry Department, and Prof. Yair Reisner of the Immunology Department, together with Prof. Berrebi of Rechovot's Kaplan Hospital, adopted an approach that fastens the enzyme allinase onto a specific antibody already in clinical use, Rituximab, designed to target and lock on to the surface of certain types of cancer cells such as lymphoma. When administered alone, Rituximab serves as a marker and docking point for the body's own immune system to kill the cancer cell. The Institute team demonstrated that cancer cells could be destroyed more efficiently by binding allinase to this antibody and triggering the production of allicin while the allinase is attached to the cancer cell.
Although other approaches use a method that directly binds anti-cancer drug molecules to an antibody, this study applied a method Prof. Mirelman refers to as "weaponizing" an antibody, so called because it affords the continuous production and delivery of cancer-killing "bullets": the allinase that is bonded to the Rituximab sits on the target cell and continuously reacts with alliin molecules that are injected at intervals, producing a steady supply of allicin to penetrate and kill the cancer.
In the war on cancer, in addition to the aforementioned "ground troops" armed with the latest weapons, there are also efforts underway to disrupt enemy communications.
In a study published recently in the Proceedings of the National Academy of Sciences (USA), a team of Weizmann Institute scientists demonstrated how the right combination might form a web that destroys the cancer cell's communication network, ultimately demobilizing the cell. Three decades of intensive cancer research led to the identification of a family of receptors, known as HER, that sit antenna-like on the outside of the cell wall and are implicated in certain types of cancer. A team of researchers under Professor Yosef Yarden, Dean of the Weizmann Institute's Feinberg Graduate School and a professor in the Institute's Biological Regulation Department, and Prof. Michael Sela, former president of the Weizmann Institute of Science and currently a professor in the Institute's Immunology Department, teamed up to create a strategy for the customization of antibodies that work independently to engage these cancer-specific receptors and shut down the attendant signaling network.
The study was carried out in cooperation with researchers from Targeted Molecular Diagnostics, Westmont, IL, USA.
Finally, in the campaign against cancer, Weizmann scientists have discovered how the enemy's undercover agents have been infiltrating the ranks.
Disease agents called retroviruses, responsible for causing AIDS and cancers such as leukemia, manage to sneak into cells with the help of special protein assemblies scattered all over their surfaces. These retrovirus surface proteins cause the membrane envelope of the virus to fuse with the membrane of the cell, spilling virus RNA into the cell to wreak damage. Now, a team of scientists at the Weizmann Institute and the Max Planck Institute for Biochemistry has obtained a close-up 3-D portrait of the large protein complex on the virus that enables its entry into the cell. Their work appeared in the Proceedings of the National Academy of Sciences in March.
Dr. Deborah Fass of the Weizmann Institute's Structural Biology Department and student Nathan Zauberman teamed up with scientists from Max Planck's Molecular Structural Biology Department in Martinsried, Germany. They saw strong evidence that the protein complex undergoes a radical change in shape and arrangement of its component parts as it attaches to cells and initiates membrane fusion. Fass was able to see how a smaller protein piece she had previously isolated and analyzed by crystallization fit into the whole, giving her further clues as to how the virus locks onto the cell membrane.
[For more 2005 reports on Israeli advances in the war against cancer, see:
1. "Israeli Study - Turmeric Prevents Colon Cancer"
2. "Israeli Scientists Develop 'Micro Missile' to Combat Cancer"
3. "Israeli Technology to Help Breast Cancer Patients"
4. "Fighting Cancer With a Tree"]