Cleveland Clinic researchers have started phase I trial for a vaccine aimed at eventually preventing triple-negative breast cancer, the most aggressive and lethal form of the disease.
The US Food and Drug Administration have already approved an investigational new drug application for the vaccine, which permits Cleveland Clinic and partner Anixa Biosciences, Inc. to launch the study.
“This vaccine approach represents a potential new way to control breast cancer,” said Vincent Tuohy, the primary inventor of the vaccine and staff immunologist at Cleveland Clinic’s Lerner Research Institute.
Why is it Important?
Despite representing only about 12-15 percent of all breast cancers, triple-negative breast cancer accounts for a disproportionately higher percentage of breast cancer deaths and has a higher rate of recurrence. This form of breast cancer is twice as likely to occur in African-American women, and approximately 70 percent to 80 percent of the breast tumors that occur in women with mutations in the BRCA1 genes are triple-negative breast cancer. So there is a great need for improved treatments for triple-negative breast cancer, which does not have biological characteristics that typically respond to hormonal or targeted therapies.
Vaccine trial: Phase 1
The phase I trial is designed to determine the maximum tolerated dose of the vaccine in patients with early-stage triple-negative breast cancer and to characterize and optimie the body’s immune response. The new study at Cleveland Clinic will include 18 to 24 patients who have completed treatment for early-stage triple-negative breast cancer within the past three years and are currently tumor-free but at high risk for recurrence. During the course of the study, participants will receive three vaccinations, each two weeks apart and will be closely monitored for side effects and immune response. The study is estimated to be completed in September 2022.
Vaccine trial: Subsequent phases
In the subsequent trials, healthy, cancer-free women will be enrolled to evaluate whether the vaccine can prevent high-risk patients from developing this type of breast cancer. The study will be done on women who are at high risk for developing breast cancer who have decided to undergo voluntary bilateral mastectomy to lower their risk. Typically, those women carry mutations in either the BRCA1 or BRCA2 gene and are therefore at risk of developing triple-negative breast cancer or have high familial risk for any form of breast cancer.
“We are hopeful that this research will lead to more advanced trials to determine the effectiveness of the vaccine against this highly aggressive type of breast cancer,” said G. Thomas Budd, of Cleveland Clinic’s Taussig Cancer Institute and principal investigator of the study. “Long term, we are hoping that this can be a true preventive vaccine that would be administered to healthy women to prevent them from developing triple-negative breast cancer, the form of breast cancer for which we have the least effective treatments.”
“The long-term objective of this research is to determine if this vaccine can prevent breast cancer before it occurs, particularly the more aggressive forms of this disease that predominate in high-risk women,” said Dr. Tuohy who is as inventor on the technology, which Cleveland Clinic exclusively licensed to Anixa Biosciences, Inc. He will receive a portion of commercialization revenues received by Cleveland Clinic for this technology and also holds personal equity in the company.
The investigational vaccine targets a breast-specific lactation protein, α-lactalbumin, which is no longer found post-lactation in normal, aging tissues but is present in the majority of triple-negative breast cancers. Activating the immune system against this “retired” protein provides pre-emptive immune protection against emerging breast tumors that express α-lactalbumin. The vaccine also contains an adjuvant that activates an innate immune response that allows the immune system to mount a response against emerging tumors to prevent them from growing.
The pre-clinical research, led by Dr. Tuohy, had showed that activating the immune system against the α-lactalbumin protein was safe and effective in preventing breast tumors in mice. The research also found that a single vaccination could prevent breast tumors from occurring in mouse models, while also inhibiting the growth of already existing breast tumors. The research, originally published in Nature Medicine, was funded in part by philanthropic gifts from more than 20,000 people over the last 12 years.
Transforming cancer research
“This vaccine strategy has the potential to be applied to other tumor types,” added Dr. Tuohy. “Our translational research program focuses on developing vaccines that prevent diseases we confront with age, like breast, ovarian and endometrial cancers. If successful, these vaccines have the potential to transform the way we control adult-onset cancers and enhance life expectancy in a manner similar to the impact that the childhood vaccination program has had.”