Is the magic bullet about to start killing?
Added: (Thu Aug 02 2001)
Pressbox (Press Release) -
Magic bullets, antibodies fused to isotopes or toxins have received considerable attention as candidate strategies for novel anti-cancer treatments. The concept of this approach is highly exciting since it will allow antibodies to deliver death sentences to cancer cells wherever they may be hiding in the body.
The magic bullet approach is particularly attractive for the treatment of metastatic or residual cancer and untreatable tumors.
Significant problems have however arisen due to the poor penetration of solid tumors by large antibodies. This has been tackled by engineering small Fv fragments of targeting antibodies. A second shortcoming is related to antibody toxicity.
Therapeutic margins have been dramatically improved over recent years through the development of mouse:human chimeric, or fully human antibodies which avoid the problem of human anti-mouse antibody production, however non-specific toxicity resulting from antibody targeting of the liver has also been reported. Lowering non-specific toxicity may be allow the full potential of magic bullets to be unleashed.
According to new data overviewed in yesterdays edition of TherapeuticAdvances, a leading bulletin of cutting edge technology with pharmaceutical potential this may shortly be possible.
Researchers at the NIH have shown that this is dependent on the isoelectric point of the Fv fragment and that engineering peptides with reduced isoelectric points can dramatically reduce toxicity without affecting anti-cancer efficacy.
According to LeadDiscovery consultants "this advance may represent a small conceptual step forward, however it may offer a major leap forward for the clinical usefulness of magic bullets". The recent approval of magic bullets for certain leukemias and lymphomas signalled a new dawn for cancer treatment. Hopefully recent advances will signal an era in which a wider variety of solid tumors can be safely targeted by magic bullets
For information on in-depth analyses of this and related work visit the LeadDiscovery website at http://www.leaddiscovery.co.uk/target-discovery/therapeuticadvances.html.
LeadDiscovery is a leading Sussex based firm of drug discovery, development and commercialization consultants whose aim is to combine a background in the pharmaceutical industry with an internet platform to help academic and biotech based research groups to exploit their technology.
A protac was engineered, fusing IkappaBalpha phosphopeptide at one end, which binds the ubiquitin complex, and ovalicin at the other end which binds MetAP-2. This chimera was able to target methionine aminopeptidase-2 to the ubiquitin complex resulting in its ubiquitination and degradation.
According to LeadDiscovery consultants "This particular strategy may offer a novel way of blocking angiogenesis, a vital component of tumor progression. More generally however, Protac technology could be conceivably used to target any intracellular protein if a corresponding molecule is identified or synthesized to which it binds". This exciting technology deserves industrial attention.
For information on in-depth analyses of this and related work visit the LeadDiscovery website at http://www.leaddiscovery.co.uk/target-discovery/therapeuticadvances.html.
LeadDiscovery is a leading Sussex based firm of drug discovery, development and commercialization consultants whose aim is to combine a background in the pharmaceutical industry with an internet platform to help academic and biotech based research groups to exploit their technology.