LIVERMORE , Calif. — Prostate, breast and other cancer patients may be offered
a new, stauncher targeted drug delivery system to treat their diseases in the
next decade.
Using atomic force microscopy and computer simulations,
researchers from Lawrence Livermore National Laboratory
and the UC Davis Cancer Center have unveiled a new
and reliable technique to characterize the binding
interaction of multivalent molecules designed for
targeted drug delivery in cancer treatment.
The Livermore team used atomic force microscopy
(AFM) to measure the binding forces between several
single-chain antibody fragments and Mucin1 peptide.
Mucin1 is commonly found in large quantities in a
variety of epithelial cells in the human body, and
one of its specific forms is a characteristic marker
for prostate, breast, colon, lung, gastric and pancreatic
cancers. Binding between Mucin1 and antibodies recognizing
the marker is critical to targeted drug delivery
for cancer patients.
“We found a very good way of quantifying the drug
binding affinity, which determines the drug's efficiency,” said
Aleksandr Noy, a researcher in LLNL's Chemical Biology
and Nuclear Sciences Division (CBDN), who along with
CBDN postdoctoral student Todd Sulchek is the lead
author of a paper that appears in the Proceedings
of the National Academy of Sciences online edition
for the week of Oct. 31-Nov. 4. “Not only does this
technique aid doctors in delivering targeted drugs
in cancer treatment, but it also may benefit the
Laboratory's efforts evaluating antibodies and designing
better binding molecules for biosensors that play
such a critical role in national security.”
Noy said the technique could be applied to other
types of cancer including colon, lung, gastric and
pancreatic.
The UC Davis collaborators are one of the leading
groups in the radioimmunotherapeutics development
field. The group has had promising outcomes from
testing this new generation of enhanced radioimmunotherapeutics.
The team's results open significant new opportunities
for researchers in areas ranging from drug design
to biophysics.
“We developed a technique that could help to optimize
binding affinity, so for this particular application
we have looked at super-binders targeting cancer
cells,” Noy said. “If the program wants to create
a super-binder for a pathogen assay, the technology
and the results will be directly applicable.”
In addition to Noy and Sulchek, Livermore scientists
Raymond Friddle, Kevin Langry, Edmond Lau, Timothy
Ratto and Michael Colvin (who now works at UC Merced)
collaborated with UC Davis Cancer Center researchers
Huguette Albrecht and Sally DeNardo.
Founded in 1952, Lawrence Livermore National Laboratory
has a mission to ensure national security and apply
science and technology to the important issues of
our time. Lawrence Livermore National Laboratory
is managed by the University of California for the
U.S. Department of Energy's National Nuclear Security
Administration.
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