Novel lipoplex nanoparticle to be used in 1st human trial treating
advanced solid cancer
Washington D.C. -- The first clinical trial of a biologic
nanoparticle designed to give back to cancer patients the tumor-
busting gene they have lost is expected to start in September at
Georgetown University Medical Center.
The phase I clinical study will enroll 20 patients with advanced
solid cancers (including most common tumor types), and is the
culmination of more than a decade of work by a team of researchers
led by Professor Esther H. Chang, Ph.D. at the Lombardi
Comprehensive Cancer Center.

Their research has led to development of a tiny structure --
measuring a millionth of an inch across -- that resembles a virus
particle that can penetrate deeply into the tumor and move
efficiently into cells. The device is a "liposome" -- a microscopic
globule made of lipids -- that is spiked on the outside with
antibody molecules that will seek out, bind to, and then enter
cancer cells including metastases wherever they hide in the body.
These molecules bind to the receptor for transferrin that is present
in high numbers on cancer cells.

Once inside, the nanoparticle, which the researchers call
a "immunolipoplex," will deliver its payload -- the p53 gene whose
protein helps to signal cells to self-destruct when they have the
kind of genetic damage characterized by cancer and by cancer
therapies.

More than half of all cancer patients have cancer cells that have
lost normal functioning of the p53 gene, so-called "guardian of the
genome," and the Georgetown researchers believe that restoring the
gene will improve the tumor-killing ability of traditional
treatments.

"We are excited about the promise this nanoparticle has shown in
animal tumor models, and are anxious to offer it to patients," said
Chang, Professor in the Department of Oncology and Co-director of
the Molecular Targets & Developmental Therapeutics Program at
Georgetown.

The federal Food and Drug Administration granted approval for the
trial to begin in late July. The work is being sponsored by grants
from the National Institutes of Health and private foundations.
Additional support comes from SynerGene Therapeutics, a biotech
research firm with which Chang collaborates.

John Marshall, M.D., Director of Developmental Therapeutics and GI
Oncology at Georgetown, will serve as the trial's principal
investigator.

The researchers believe that immunolipoplex represents an advance
over the viral "vectors" that have been used to deliver gene
therapy, because these liposomes do not produce the kinds of
immunologic response seen when disabled viruses are used to carry
the payload. They also say that the nanoparticle is of a small
uniform size and consistency, and has been proven to work in animals
bearing tumor.

In preclinical research, Chang and long-term research colleague
Kathleen Pirollo, Ph.D. have found that these nanoparticles
substantially improve the tumor-fighting power of both chemotherapy
and radiation therapy. These agents work synergistically with
traditional therapies because the newly restored p53 protein helps
push cancer cells that are now damaged to self-destruct.

"We believe this approach will make it difficult for the cancer
cells to become resistant to therapy," Chang said. "As a result,
cancers treated with these liposomal formulations should be less
likely to recur after therapy is complete."

For example, use of these p53-loaded liposomes in combination with
radiation therapy eliminated prostate and head and neck tumors in
mice, which then survived cancer-free for more than 200 days --
until they all died of old age. Similar promising results were seen
when the nanoparticles were combined with chemotherapy to treat
animal models of melanoma and aggressive breast cancer.

Among the solid tumors approved for testing in the clinical trial
are head and neck, prostate, pancreatic, breast, bladder, colon,
cervical, brain, melanoma, liver and lung cancers.

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