Press releases
08/04/2008
Data on AS1411 action in breast cancer cells published in Cancer Research
London, UK, 8 April 2008 – Cancer drug developer Antisoma plc (LSE: ASM; USOTC:ATSMY) today announces the publication of data on the selective killing of breast cancer cells by Antisoma’s nucleolin-targeting aptamer AS1411. The work was carried out by Professor Daniel Fernandes and colleagues at the Medical University of South Carolina (MUSC) and is published in the April issue of the journal Cancer Research.
Professor Fernandes and his team compared the effects of AS1411 on a breast cancer cell line and on a normal breast cell line. A 5 µmol/l dose clearly inhibited the growth of breast cancer cells. In contrast, a four-fold higher dose had no discernible effect on normal breast cells. The selective action of AS1411 on cancer cells correlated with two differences between cancer cells and normal cells. First, cancer cells expressed considerably more nucleolin in their cytoplasm. Second, cancer cells internalised more AS1411.
The authors investigated how AS1411 kills breast cancer cells once it is internalised. They showed that the drug down-regulates the messenger RNA encoding Bcl-2, a protein that allows cancer cells to avoid death by apoptosis. Previous work from Professor Fernandes’ group has shown that nucleolin plays an important role in maintaining Bcl-2 levels in certain cancer cells. It does this by binding to and stabilising Bcl-2 messenger RNA. AS1411 acts as a ‘molecular decoy,’ binding nucleolin and preventing its interaction with Bcl-2 messenger RNA. This leads to a fall in Bcl-2 messenger RNA levels, a consequent fall in the level of the Bcl-2 protein and, ultimately, apoptosis.
Professor Fernandes said: “We continue to gain new insights into how AS1411 acts though nucleolin to induce the death of tumour cells. Ability to avoid apoptosis is a fundamental property of cancer cells, and so the discovery that AS1411 interferes with the Bcl-2 pathway that protects cancer cells from apoptosis is an exciting observation.”
Dr Ursula Ney, Antisoma’s Chief Operating Officer, added: “These encouraging findings suggest that AS1411 could have potential in breast cancer, which is among the most common cancers worldwide.”
AS1411 is currently in a randomised phase II study in acute myeloid leukaemia, with further phase II studies planned in renal and other cancers.
Enquiries:
Glyn Edwards, CEO
Daniel Elger, Director of Communications
Antisoma plc
+44 (0)7909 915 068
Mark Court/Lisa Baderoon/Rebecca Skye Dietrich
Buchanan Communications
+44 (0)20 7466 5000
Brian Korb
The Trout Group
+1 646 378 2923
Except for the historical information presented, certain matters discussed in this statement are forward looking statements that are subject to a number of risks and uncertainties that could cause actual results to differ materially from results, performance or achievements expressed or implied by such statements. These risks and uncertainties may be associated with product discovery and development, including statements regarding the company's clinical development programmes, the expected timing of clinical trials and regulatory filings. Such statements are based on management's current expectations, but actual results may differ materially.
Notes for Editors:
Background on AS1411
Aptamers are short
pieces of DNA or RNA that can fold into stable, three-dimensional
structures capable of interacting with particular target proteins.
AS1411 is the first aptamer to be tested as a treatment for cancer.
It binds to the protein nucleolin, which is found on the surface of
cancer cells. It is then internalised and has been shown to kill
cancer cells from a variety of cell lines. The drug has also shown
anti-cancer effects in animal models and promising signs of
anti-cancer activity in the clinic. AS1411 was originally developed
by Dr Paula Bates, Dr John Trent and Prof. Donald Miller at the
University of Alabama and then at the University of Louisville.
Antisoma added AS1411 to its pipeline when it acquired the
Louisville-based company Aptamera Inc. in February 2005.
Background on Antisoma
Headquartered in
London, UK, Antisoma is a biopharmaceutical company that develops
novel products for the treatment of cancer. Antisoma fills its
development pipeline by acquiring promising new product candidates
from internationally recognised academic or cancer research
institutions. Its core activity is the preclinical and clinical
development of these drug candidates. Please visit
www.antisoma.com for further
information about Antisoma.
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