Taking Off the Gloves In The Fight Against Breast Cancer
Breast cancer is one of the most commonly diagnosed cancers among American women. About 1 in 8 (12%) women in the U.S. will develop invasive breast cancer during their lifetime. A researcher in Kent State University’s College of Arts and Sciences is doing his part to halt breast cancer in its tracks.
Dr. Gary Koski, Associate Professor in the Department of Biological Sciences, is collaborating with his long-time colleague Dr. Brian Czerniecki, M.D., head of Moffitt Cancer Center’s breast oncology program in Tampa, Florida, and Dr. Mary Disis of the University of Washington-Seattle, on revolutionary new ways to prevent and treat breast cancer through immunization. The researchers received a $10 million grant from the Department of Defense (DoD) to fund clinical trials of a new vaccine.
Since 2004, they’ve immunized over 110 patients who were diagnosed with an early, pre-invasive form of breast cancer called ductal carcinoma in situ (DCIS) using a vaccine targeting the human epidermal growth factor receptor 2 (HER-2) protein, present on about a third of all breast cancers. The American Cancer Society estimates that there are about 250,000 cases of breast cancer diagnosed in the U.S. each year and around 60,000 of these are DCIS.
“Currently we have three accepted modalities for treating cancer,” Koski said. “They are surgery, radiation therapy, surgery and chemotherapy, which in the field we kind of euphemistically refer to as slash, burn, and poison. When you consider some of the morbidities that are associated with these treatments are very unpleasant, we are sort of crying out for a new and better way to treat cancer.”
HOW THE VACCINE WORKS
Besides the work the researchers have done with DCIS, they now have trials opening on invasive HER-2-expressing breast cancer. These are geared toward preventing recurrence after the tumor is surgically removed. They are also laying the groundwork for new vaccines against other breast cancer types that do not produce the HER-2 protein such as so-called “triple-negative” breast cancers. But, the vaccines are a few years away from becoming a normal treatment as it will be five to ten years before you'll see the first approvals of vaccines. The first ones will likely be for preventing reoccurrence.
“The vaccine that we’ve developed is rather unique,” Koski said. “We’re taking a type of white blood cell from the patient, called dendritic cells, and we’re culturing them for a short time outside the body. We’re activating them, loading them up with proteins that come from the tumor cells (such as HER-2) and then we deliver them back to the patient. The dendritic cell, in a sense, teaches the immune system to attack certain proteins that are present on the breast cancer cells.”
The vaccines work like a vaccine would work against a virus, by revving up the immune system against certain proteins the cancer cells have on them and trying to prevent disease from developing or prevent the disease from reoccurring. The approach tricks the dendritic cells to see a tumor as it would a bacteria or virus. It uses the patient’s own dendritic cell precursors, requires four injections with few side effects, and has production costs competitive with other treatment modalities.
Koski’s role on the project is to help determine the mechanisms by which the vaccine is working and to identify low-toxicity, targeted anti-cancer drugs that will work in concert with vaccination to increase its efficacy. In their first clinical trial testing of the vaccine on 27 recipients, five showed no evaluable disease at time of surgery, and tumors in half of the 22 remaining patients showed profound suppression of the HER-2 protein. This loss is considered advantageous because HER-2 is known to promote tumor aggressiveness and indicates poor prognosis.
They administered the vaccine to the patient 4-6 weeks prior to the scheduled surgical resection of the tumor. After the initial trial, they have continued to refine the vaccine. “What we’ve found in treating over 110 patients is we can make the tumors go completely away in almost 30 percent of these patients with an early form of breast cancer due to their strong immune responses,” Koski said.
After the initial trial, they have continued to refine the vaccine. “What we’ve found in treating over 110 patients is we can make the tumors go completely away in almost 30 percent of these patients with an early form of breast cancer due to their strong immune responses,” Koski said.
“We’ve also tried it in slightly later stages of breast cancer and the vaccine is not as effective for later stages, so one of the things we want to do is try to improve the vaccine so that we can use it in late stages as well,” Koski said. “One of the ways we are attempting to do this is to try to find drugs, not the harsh chemotherapy that we are used to, but more benign drugs that will work in conjunction with vaccination to leverage the immune response and to improve the responsiveness so we can go into later stage of disease,” Koski said.
The researchers are also highly interested in moving onto treating other tumor types. The proteins on the breast cancer cells that they are targeting in their vaccine are also expressed on many other types of tumors, for example gastric cancer, ovarian cancer, esophageal cancer, prostate cancer, and non-small cell lung cancer.
“At the conclusion of the phase II clinical trials funded by the DoD, we hope to have sufficient data to design and raise funds for a phase III trial that will establish our approach as an FDA-approved treatment option for women with HER2-expressing breast cancer,” Koski said. “With luck, that could happen 6-8 years from now.”