Cyanide shows promise in fight against cancer
Posted: Wednesday, September 06, 2000
[London, 6 September 2000] Researchers at London’s Imperial College, funded by UK-based cancer
company Antisoma plc, have harnessed a cyanide-generating system, used by plants as a natural defence
mechanism to fend off insects, as a potential weapon against cancer.
According to promising data to be presented at the British Association’s Festival of Science meeting,
“Creating Sparks,” which opens in London today, the scientists have mimicked a natural method of
protection used by plants like the African potato and the hydrangea. The plants contain an enzyme, called
linamarase, which is capable of generating cyanide when animals or insects cause damage to the plant,
thereby deterring further attacks. Scientists have attached the enzyme to a cancer-seeking antibody
capable of recognising a protein found only in certain cancers. The molecule formed from the combined
antibody and enzyme has been shown to generate small amounts of cancer-killing cyanide when presented
with a separately administered, natural, non-toxic chemical substance.
“We have demonstrated that this system is able to specifically kill tumour cells by cyanide intoxication,” says
Dr Mahendra Deonarain of Imperial College’s Department of Biochemistry in London.
Although at an early stage, the method -- known as AGENT (Antibody Guided Enzyme Nitrile Therapy) --
could eventually lead to a safe and effective way of treating cancer which acts only on cancerous cells and
leaves healthy tissue unharmed. Unlike existing cancer-killing treatments, which can cease to be effective as
cells develop resistance, cancer cells are unable to resist the effects of cyanide.
Despite the deadly nature of cyanide, the amount generated by the technique is only sufficient to kill the
specific cancer cell targeted by the combined enzyme-antibody molecule. A natural enzyme produced in the
human liver will detoxify any cyanide that leaks away from the tumour.
“At this stage of the research, we have yet to determine the optimum molecule. However, we have
demonstrated the concept of cyanide-targeted tumour cell killing and are actively working to develop a
higher potency system able to act on a variety of cancer types,” Deonarain will tell the conference.
Professor Agamemnon Epenetos, Chief Scientific Officer at Antisoma plc added: “This is a fascinating use
for a natural defence mechanism, one of several projects that Antisoma is funding as it seeks to broaden its
early stage cancer pipeline.”
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Notes
Antisoma is a biopharmaceutical company developing novel products for the treatment of cancer. The
Company’s strategy is to use its drug development experience to produce safer and more effective tumour
targeting therapies for commercialisation by pharmaceutical partners. The Company’s core competence is
the conduct of rapid, cost-effective, semi-virtual drug development. Antisoma acquires the rights to promising
new product candidates through partnerships with internationally recognised academic or cancer research
institutions. These include the lead product candidate, Theragyn, which was licensed from the Imperial
Cancer Research Fund.
The Company’s particular focus is the use of monoclonal antibodies to target tumour cells while leaving
healthy cells unharmed. The lead product, Theragyn, is currently in a Phase III study as adjuvant treatment
for ovarian cancer, with designated Orphan Drug status in the US. Abbott Laboratories have a worldwide
exclusive licence to develop, market and sell the product.
Antisoma’s therapeutic product candidates are:
Product candidate Indication(s) Current stage of development
Theragyn Ovarian cancer Phase III
Gastric cancer Phase II
Therex Breast cancer Phase I
TheraFab Lung cancer Pre-clinical
AngioMab Brain cancer Pre-clinical
Other solid tumours Pre-clinical
Targeted apoptosis Cancer Pre-clinical
Immunotherapy Cancer Pre-clinical