Julia Chen

http://www.sciencedaily.com/releases/2005/05/050503104540.htm



Allicin In Wonderland: Scientists 'Weaponize' An Antibody To Deliver Continuous
Attacks On Cancer Cells



In a recent study published in Molecular Cancer Therapeutics, researchers at
the Weizmann Institute of Science paired the active ingredient of a garden
remedy with advanced bio-technology to deliver a powerful punch against cancer.
The cancer killing effectiveness lies in their technique of arming a
cancer-targeting antibody with the destructive potential of the dietary
molecule otherwise known as "allicin."





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, 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
arming this antibody: They first chemically bound alliinase to Rituximab and
then injected this conjugate into mice that had been implanted with human
lymphoma cancer cells. As predicted, the Rituximab, 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 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. 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 Rituximab 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.