UNMC 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 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.
 |
James Talmadge, Ph.D. |
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. 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, will enter patients into the study at UNMC.
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 would 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 body’s immune system,” Dr. Cowan said.
The study is unique, in that it will establish when during the course of a patient’s treatment it is best to introduce the vaccine so it will be most effective, Dr. Talmadge said. 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, who’s been working with breast cancer vaccines for the past five years. “I’m 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 don’t. We don’t understand why the vaccine doesn’t 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 patient’s 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. Gabrilovich’s and Dr. Talmadge’s 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