The University of Nebraska Medical Center has received a two-year, $500,000
grant to conduct a clinical breast cancer study to test the safety and
effectiveness of a vaccine in combination with surgery and chemotherapy.
The funding was awarded by Avon and the U.S. National Cancer Institute
Progress for Patients Program.
UNMC researchers expect to begin enrolling patients sometime in January.
An estimated 267,000 new cases of breast cancer are expected to occur
among women in the United States during 2003, resulting in an estimated
39,800 deaths.
The vaccine, known as INGN 225, a genetically engineered tumor vaccine,
will be evaluated to treat patients with breast cancer. Two U.S. National
Cancer Institute-designated cancer centers are participating in the gene
therapy trial.
James Talmadge, Ph.D., UNMC professor of pathology and microbiology,
is principal investigator of the study. Patients will be entered into the
study at UNMC by Ken Cowan, M.D., Ph.D., director of UNMC Eppley Cancer
Center, and Elizabeth Reed, M.D., associate professor of internal medicine
and director of the UNMC Breast Cancer Program.
H. Lee Moffitt Cancer Center in Tampa, Fla., also will participate in
the study by preparing the vaccine and participating in immunologic evaluations.
The vaccine is manufactured by Introgen Therapeutics, Inc., of Austin,
Texas.
Dr. Cowan said the vaccine will provide a surveillance system, which
researchers hope will eradicate any tumor cells left following treatment.
The vaccine in essence would mop up any tumor cells that are left behind
using the bodys immune system, Dr. Cowan said.
Dr. Talmadge said the uniqueness of the study is that it will establish
when during the course of a patients treatment it is best to introduce
the vaccine so it will be most effective. He knows of no other studies
looking at the timing of introducing cancer vaccines during treatment.
He said most vaccine protocols are begun following several cycles of chemotherapy.
This is a unique and very important question, said Dr. Talmadge, whos
been working with breast cancer vaccines for the last five years. Im
pleased with the protocol that we developed and its potential to help advance
vaccine therapy for cancer. If the question of vaccine timing relative
to primary chemotherapy is successfully addressed, the results could be
relevant to other tumor types undergoing vaccine therapy.
In other studies, we accept patients independent of the extent of prior
therapy and so some respond, and some dont. We dont understand why the
vaccine doesnt work with all patients and the variability in the extent
of prior therapy likely contributes to the different response rates, Dr.
Talmadge said.
Researchers theorize that vaccinating patients earlier may result in
a higher immune response to the vaccine. The vaccine is given with the
hope of preventing recurrence of breast cancer.
A better understanding of when to give the vaccine relative to primary
therapy should improve the patients immune response to the therapy and
enable us to move on to more effective protocols and vaccines, Dr. Talmadge
said.
In the randomized study, which will begin enrollment in January, one
group of patients will receive a total of four vaccine injections during
and following chemotherapy, and the other will receive a total of four
vaccinations following completion of chemotherapy and radiation. Fifty
patients, with stage II or stage III breast cancer, who have not yet begun
surgery, chemotherapy and/or radiation treatment, may be enrolled for the
study. Stage II and III breast cancer patients are considered those with
four or more lymph nodes with metastasis, and/or a tumor the size of three
centimeters.
The vaccine was developed based on work by Dr. Dmitry Gabrilovich, associate
professor of oncology at the Moffitt Cancer Center, and Dr. David Carbone,
professor of oncology at the Vanderbilt-Ingram Cancer Center, and is exclusively
licensed to Introgen Therapeutics. Previously published pre-clinical data
from Dr. Gabrilovichs and Dr. Talmadges laboratories have shown that
animals vaccinated with p53 vectors are protected against tumor development.
INGN 225 is already being evaluated in patients with small-cell lung cancer
at Moffitt Cancer Center, in a phase I study.
Advexin therapy, recently designated as a Fast Track Program for head
and neck cancer by the FDA, has been evaluated in numerous clinical studies
including phase 3 studies for head and neck cancer, as well as phase 1
and 2 studies for various types of cancer. In these studies, Advexin
uses the p53 protector gene (guardian of the genome) to directly kill
cancer cells and to stop tumor growth, without harming normal cells.