U.S. Army Medical Research and Materiel Command
Point of Contact:
Chuck Dasey, (301) 619-7071
July 20, 2000
For Immediate Release:
Vaccine Studies Demonstrate Promise of Immunotherapy Both to Treat Breast Cancer and Prevent Recurrence
Research Results from "Era of Hope" Department of Defense Breast Cancer Research Program Meeting
ATLANTA, June 11, 2000 - The notion of developing vaccines to treat and prevent cancer has tantalized scientists for many years. Two studies presented at the "Era of Hope" Department of Defense Breast Cancer Research Program meeting exemplify different but equally promising approaches to the development of cancer vaccines. Both approaches capitalize on recent advances in scientific understanding of the body's natural disease-fighting mechanisms.
New Vaccine Approach Aims to Prevent Breast Cancer Recurrence
Researchers have developed an experimental cancer vaccine that for the first time generates an immune response against a protein overexpressed in some patients with breast and other cancers by stimulating a response to so-called helper T cells. Previous vaccine studies have concentrated on stimulating killer T cells.
"This is one of the first trials to show that it's possible to generate an immune response to a cancer protein by immunizing patients with fragments of the protein," said Mary L. Disis, M.D., associate professor of medicine, University of Washington, Seattle, WA. "It is also the first step toward the long-term goal of developing an affordable and hopefully practical vaccine to prevent cancer recurrence."
The vaccine is made from fragments of HER-2/neu, a protein that is a tumor antigen, which means it can generate an immune response in a cancer patient. Dr. Disis and her colleagues chose to test HER-2/neu as a vaccine after preliminary studies found that some patients had pre-existing low levels of immunity to the protein. They hypothesized that a vaccine that boosted this pre-existing immunity might induce an anti-tumor effect.
This study, designed to evaluate the experimental vaccine's safety and ability to generate an immune response, included 64 patients - all of whom had completed treatment for stage III or IV breast, ovarian and lung cancer and either showed no evidence of disease or were stable on hormonal therapy. Thirty-eight patients completed the course of six monthly vaccinations. The others did not complete the study due to disease progression, which required a return to standard treatment.
Ninety percent of the patients who got all six vaccinations developed an immune response to the protein fragments, known as peptides, and 75% developed an immune response to the protein itself. The vaccine stimulated the production of helper T cells, which "rev up" the production of other immune system cells that then attack and kill invaders. (Killer T cells, by contrast, directly attack and kill invaders.) The vaccine was totally nontoxic, reported Dr. Disis.
After the course of vaccinations was completed, the researchers continued to monitor a subset of patients - who volunteered for long-term follow-up - to see how long their immunity to HER-2/neu persisted. The researchers noted that immune responses occurred in some patients who had not shown a response after receiving all six vaccinations; in addition, others experienced an increased immune response during the long-term follow up period. Four patients have retained immunity for two years or longer after they were vaccinated.
"These follow-up data suggest that the immune system may be able to 'remember' and respond to the protein long after vaccination has taken place - the hallmark of a successful vaccine," said Dr. Disis. However, she acknowledges that it will take a larger and longer clinical study to determine whether this vaccine can indeed create long-term "immunologic memory" and stop cancer from recurring.
The eventual goal of Dr. Disis and her colleagues is to develop a vaccine that could be used routinely to prevent cancer recurrence. In the process, the researchers are currently testing other formulations of the vaccine, using different adjuvants (helper substances), to see which one generates the most effective immune response against the HER-2/neu protein. The most promising formulation will be tested for effectiveness in preventing cancer recurrence in patients with stage III breast cancer who are at high risk for relapse.
Novel Delivery of Dendritic Cells Shows Promising Results in Animal Study
In data presented here by another research group, significant regression of breast tumors occurred in mice treated with an experimental cancer vaccine. For the first time, researchers injected special immune system cells, called dendritic cells, directly into breast tumors. Dendritic cells are powerful immune system stimulants, capable of "turning on" killer T cells that then multiply and attack cancerous cells both in the affected organ and elsewhere in the body.
"The next step is to find the best way of translating these findings into a human clinical trial," said Christopher J. Kirk, Ph.D., a research fellow in the Tumor Immunology Program, University of Michigan Medical Center, Ann Arbor, MI. "If this strategy proves effective in humans, the ultimate hope is that immunotherapy with dendritic cells could be used in conjunction with chemotherapy, potentially lowering the chemotherapy doses and thereby reducing side effects while improving efficacy."
Dendritic cells are scavengers, ingesting tumor cells that are dying as a result of a process known as apoptosis or programmed cell death. The dendritic cells then present pieces of the digested tumor proteins to T cells, which stimulates an immune response, particularly by the killer T cells that multiply and attack tumor cells.
In this study, the researchers gave four intratumoral injections of dendritic cells to 25 mice. In five of the 25 treated mice, tumors regressed completely for more than three months and new tumors grafted into the same animals did not grow. In the remaining mice, tumor growth was reduced by two thirds compared with control mice. The researchers then gave two injections of dendritic cells combined with tumor necrosis factor alpha (TNF-a), a protein that promotes cell death, directly into breast tumors in another 10 mice. This time, tumors were eliminated in half of the treated mice, and overall tumor growth was reduced by approximately 80% compared with control mice.
In a preliminary study to test the feasibility of this approach in humans, six patients with advanced breast cancer are receiving intratumoral injections of dendritic cells once a week for three weeks. (TNF-a cannot be given to people because it produces severe side effects. The researchers are exploring other potential agents that can safely be given to patients to boost the anti-tumor effect of dendritic cells by causing tumor apoptosis.)
In other studies of cancer vaccines using dendritic cells, the cells have been injected into patients' skin, blood or lymph nodes. That approach requires first performing a biopsy to remove tumor cells from the patient; then the tumor cells are killed and "fed" to the dendritic cells in the laboratory. Intratumoral injection of the dendritic cells makes these preliminary steps unnecessary, explained Dr. Kirk.
Using dendritic cells to make a cancer vaccine for humans is a labor-intensive process. The cells must be derived from the patient's own white blood cells (otherwise the patient's immune system will perceive them as "foreign" and reject them). The white blood cells are grown in the laboratory with proteins that promote the growth of dendritic cells.
"Era of Hope" is a forum for the presentation of research supported by the U.S. Department of Defense's Breast Cancer Research Program (BCRP), an unprecedented partnership between the military, scientists, clinicians, and breast cancer survivors. Since 1992, the BCRP has been working to prevent and cure breast cancer by fostering new directions in research, addressing underserved populations and issues, encouraging the work of new and young scientists and inviting the voice of breast cancer survivors to be heard in all aspects of the program. One of 53 congressional research programs managed by the U.S. Army Medical Research and Materiel Command, the BCRP has received more than $1 billion to date from Congress for innovative breast cancer research.
"Vaccines Targeting the HER-2/neu (HER2) Oncoprotein in Patients with HER2 Overexpressing Cancer"
Mary L. Disis, T.A. Gooley, K.L. Knutson, M.A. Cheever, K. Rinn, D. Davis, K. Schiffman
- General Session: Sunday, June 11, 1:30 p.m. - 3:00 p.m., Grand Salon C
- Poster Session: Sunday, June 11, 6:20 p.m. - 8:00 p.m., Galleria, Posterboard AA-27
"Administration of Dendritic Cells for the Treatment of Breast Cancer"
James J. Mulé, Christopher J. Kirk
- Poster Session: Sunday, June 11, 6:20 p.m. - 8:00 p.m., Galeria, Posterboard AA-25