Question: Can you describe the need for a vaccine like this?
Answer: The vaccine we have developed has the potential to be beneficial in multiple stages of breast cancer. The most recent grant funding we received deals with the administration of this vaccine to individuals with DCIS. Although DCIS is not cancer, about 30% to 40% of individuals with DCIS will go on to develop cancer, but we typically do not know which patients with DCIS will develop cancer. These patients often are treated with surgery and endocrine therapy, and sometimes radiation therapy. Because the majority of individuals will not be diagnosed with cancer, there is a need to come up with a way to treat DCIS without the surgery, hormonal therapy and radiation therapy. Our thought — which has been observed with early cervical lesions — is that if we stimulate the immune system, the vaccine can potentially eliminate the early cancer-like lesion so that it goes away. The idea is this vaccine ultimately will protect against progression to cancer.
Q: What is included in the vaccine?
A: These are special types of vaccines. They are based upon antigens that are not microbial, so they are not virally derived. They are actually antigens that are coded by human genes that just so happen to be upregulated in cancer, and the immune system is able to recognize it.
Q: What will the study entail?
A: In our initial set of vaccine studies, we have found that we need about 6 months to immunize the individual against these antigens that are overexpressed by the cancer. The trial design we have is unique because we want to give the vaccine to patients before they are treated for DCIS. The question we will be asking is whether the vaccine eliminates the DCIS. However, we cannot do this over the course of 6 months, because standard care for DCIS is surgical removal, and 6 months is a long time to wait between diagnosis and surgery. We have to come up with an accelerated way to do this. In this trial, women diagnosed with DCIS will receive a course of four vaccinations — given every 2 weeks — followed by standard surgical resection. We additionally need to determine if the trial design needs to be a dose–response trial design in which we will escalate the dose in these individuals. We will have different groups of individuals on different doses with the purpose of generating immunity faster than we have seen achieved in past clinical trials. Once we identify the appropriate dose in these patients, we can add more individuals to the dose we find optimal.
Q: What do you expect to find?
A: This is an early-phase clinical trial. We expect to find that we can safely generate an immune response in individuals who do not have cancer. This is very important, because this is a group of individuals who are at low risk for developing cancer, and we are asking to generate an immune response against a protein that is normally found in the body. One of the central questions is whether the vaccine is safe. We have preliminary data from another 22 patients that the vaccine will be safe. We hypothesize that we will be able to safely generate an immune response. We will be looking at these primary outcomes. Secondarily, we will be looking at whether we can induce immune responses to migrate into the breast, where the precancerous lesion is, and then address whether that immune response is able to shrink or eliminate the cancer.
Q: If this trial is successful, in what type of setting will the vaccine be offered to patients?
A: There are a number of different settings. Women are essentially monitored on a regular basis using mammograms, which are primarily responsible for finding these lesions. I would anticipate that — if this vaccine is successful and a vaccine is produced — patients who have a mammographic finding will have a choice to take the vaccine with the hope that it will protect against the cancer in the future, or they can receive standard therapy with surgery, followed by hormone therapy and radiation therapy. I would assume that, if the vaccine does work, most people would choose this over surgery and radiation therapy.
Q: What is the potential for a vaccine like this to protect against other cancer types?
A: The potential exists for this vaccine to protect against other cancer types. The molecule that we are targeting in this particular case is HER2/neu, which has been a target for breast cancer in the past. A number of other cancers also express HER2/neu and, because of this, there could be the potential for protecting against other cancer types. However, the only way to rigorously test against this is through clinical trial.
Q: What will future research entail?
A: This clinical trial will enroll between 40 and 45 patients. This will give us important information about whether the vaccine will work. There are a number of things that need to occur before additional studies will be generated. The vaccine needs to be safe. It also has to generate an immune response, and that immune response has to have an impact on the cancer. Once we see this, which we hope we will, we can then design a more advanced clinical trial to see if this has any impact on the disease. In this particular case, some women would have to be on placebo and other women would receive the vaccine so that we know if women who received the vaccine had better outcomes than women who did not receive the vaccine.
Q: Is there anything else that you would like to mention?
A: We ultimately want to prevent the development of cancer, and we think that we can do this by stimulating the body’s immune system. The approaches we are using are more therapeutic than standard preventive vaccines like the flu vaccine, for example. We think the research we are doing now ultimately will lead to the development of a prevention vaccine that we can give to women in their 40s, for example, and prevent a sizable portion of breast cancer cases from occurring.
