Allicin is the product of an interaction between an enzyme, alliinase, 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. Allicin molecules can easily penetrate biological membranes and kill cells, but their potency is short-lived hence the difficulty in finding a system to deliver them to a specific site. "The medicinal value of garlic is no longer an ancient Chinese secret," says the Institute's Prof. David Mirelman. "Years of scientific research led to the identification and understanding of allicin's mode of activity and we are currently studying ways to target and deliver its toxic punch."
The team, including 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 Rehovot's Kaplan Hospital, adopted an approach that fastens the enzyme alliinase onto a specific antibody already in clinical use, Rituximabâ, designed to target and lock on to the surface of certain types of cancer cells such as lymphoma. When administered alone, Rituximabâ 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 arming this antibody: They first chemically bound alliinase to Rituximabâ and then injected this conjugate into mice that had been implanted with human lymphoma cancer cells. As predicted, the Rituximabâ, with the attached alliinase in tow, soon found and bound to the target cancer cells. Subsequently, the mice were repeatedly injected with the inert chemical alliin which, upon contact with alliinase, was processed into allicin molecules directly on the cancer cell's surface. Within three days, almost all of the human lymphoma cancer cells were destroyed in those mice treated with the conjugate and alliin, while hardly any cancer cell destruction occurred in the control mice who received the conjugate alone.
Although other approaches use a method that directly binds anti-cancer drug molecules to an antibody, this study applied a method Mirelman refers to as "weaponizing" an antibody, so called because it affords the continuous production and delivery of cancer-killing bullets: The alliinase that is bonded to the Rituximabâ 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. The production of allicin can be "turned off" by the ceasing the administration of the ammunition - alliin.
"This study was a proof of principle," says Mirelman, "demonstrating the effectiveness of this technology for the selective killing of unwanted cells." Given that the active component is a familiar dietary element, and that specific antibodies such as Rituximabâ are increasingly in clinical use, the scientists hope the way will be paved for the new technology to be developed into useful therapies.
Prof. David Mirelman's research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine; the M.D. Moross Institute for Cancer Research; Ms. Erica A. Drake, Scarsdale, NY; Mr. and Mrs. Henry Meyer, Wakefield, RI; Mr. Nathan Minzly, UK; and the late Claire Reich, Forest Hills, NY. Prof. Mirelman is the incumbent of the Besen-Brender Chair of Microbiology and Parasitology.
Journal
Molecular Cancer Therapeutics