* Human trial raises hope for promising RNAi therapy
* Treatment successfully delivered to tumors
By Julie Steenhuysen
CHICAGO, March 21 U.S. researchers have
developed tiny nanoparticle robots that can travel through a
patient's blood and into tumors where they deliver a therapy
that turns off an important cancer gene.
The finding, reported in the journal Nature on Sunday,
offers early proof that a new treatment approach called RNA
interference or RNAi might work in people.
RNA stands for ribonucleic acid -- a chemical messenger
that is emerging as a key player in the disease process.
Dozens of biotechnology and pharmaceutical companies
including Alnylam (ALNY.O), Merck (MRK.N), Pfizer (PFE.N),
Novartis NOVN.VX and Roche ROG.VX are looking for ways to
manipulate RNA to block genes that make disease-causing
proteins involved in cancer, blindness or AIDS.
But getting the treatment to the right target in the body
has presented a challenge.
A team at the California Institute of Technology in
Pasadena used nanotechnology -- the science of really small
objects -- to create tiny polymer robots covered with a protein
called transferrin that seek out a receptor or molecular
doorway on many different types of tumors.
"This is the first study to be able to go in there and show
it's doing its mechanism of action," said Mark Davis, a
professor of chemical engineering, who led the study.
"We're excited about it because there is a lot of
skepticism whenever any new technology comes in," said Davis, a
consultant to privately held Calando Pharmaceuticals Inc, which
is developing the therapy.
Other teams are using fats or lipids to deliver the therapy
to the treatment target. Pfizer last week announced a deal with
Canadian biotech Tekmira Pharmaceuticals Corp TKM.TO for this
type of delivery vehicle for its RNAi drugs, joining Roche and
In the approach used by Davis and colleagues, once the
particles find the cancer cell and get inside, they break down,
releasing small interfering RNAs or siRNAs that block a gene
that makes a cancer growth protein called ribonucleotide
"In the particle itself, we've built what we call a
chemical sensor," Davis said in a telephone interview. "When it
recognizes that it's gone inside the cell, it says OK, now it's
time to disassemble and give off the RNA."
In a phase 1 clinical trial in patients with various types
of tumors, the team gave doses of the targeted nanoparticles
four times over 21 days in a 30-minute intravenous infusion.
Tumor samples taken from three people with melanoma showed
the nanoparticles found their way inside tumor cells.
And they found evidence that the therapy had disabled
ribonucleotide reductase, suggesting the RNA had done its job.
Davis could not say whether the therapy helped shrink
tumors in the patients, but one patient did get a second cycle
of treatment, suggesting it might be. Nor could he say if there
were any safety concerns.
Davis said that part of the study will be presented at the
American Society of Clinical Oncology meeting in June.
(Editing by Doina Chiacu)