Researchers at the Cleveland Clinic have begun testing a novel vaccine against triple-negative breast cancer that uses a "retired protein" to stimulate immunity against this highly aggressive form of the disease. Investigators say the early Phase I trial, now underway, is the first step towards eventually preventing these relatively rare cancers, which disproportionately affect Black women and account for an estimated 12-15 percent of all breast cancers.
In triple-negative breast cancer, the hormonal and genetic drivers that serve as therapeutic targets in most breast cancers are lacking. So, treatment options have been few and most of these cancers progress rapidly, unchecked, to advanced stages of disease.
"The idea behind the vaccine is simply what can I do to provide preemptive immunity," said Vincent Tuohy, PhD, the vaccine's inventor and a research scientist in the Cleveland Clinic's Department of Inflammation and Immunity. By targeting alpha-lactalbumin, a natural protein in the mammary glands that plays an important role in late pregnancy and lactation, but "retires" as women age, he hopes this process will help prevent these tumors from ever forming.
Although the protein does not cause these cancers, Tuohy stressed that alpha-lactalbumin is expressed in over 70 percent of triple-negative breast cancers as they develop. The vaccine product contains both the protein and an adjuvant, designed to boost a patient's immune response to it.
The FDA approved the vaccine as an investigational new drug in December 2020, clearing the way for Tuohy and G. Thomas Budd, MD, at the Cleveland Clinic Taussig Cancer Center and the study's principal investigator, to begin vaccinating the first few women in the trial. All of the women have completed treatment for early-stage triple-negative breast cancer and are currently free of disease.
Tuohy noted that the term "retired protein" is one he made up to identify proteins that serve specific functions during natural biological processes, but later turn off as individuals age.
Proteins that fit this description, other than alpha-lactalbumin, include one for ovarian cancer, which is also apparently under study as an early vaccine candidate in collaboration with the National Cancer Institute, according to Tuohy.
Although he did not name the protein, nor did the NCI, it helps fertilize eggs, then dies out when a woman enters menopause. "And, yet in over 90 percent of ovarian cancers in post-menopausal women, we found this particular protein expressed in their tumors," he said.
This initial breast cancer study at the Cleveland Clinic takes place in a treatment setting, but the approach is "fundamentally different from other approaches," according to Robert Shoemaker, PhD, Chief of the Chemopreventive Agent Development Research Group at the NCI.
Although he chose not to comment on whether that different strategy is part of a growing trend in cancer vaccine research, when other targeted treatments fail, Shoemaker said in a written response that the NCI's main interest lies in the use of Tuohy's vaccine for cancer prevention-an idea that clearly holds promise.
"Vaccination with a retired antigen (which is re-expressed in cancers) can lead to immune elimination of tumor cells as they emerge from pre-malignant lesions," Shoemaker wrote.
As with all Phase I studies, however, the Cleveland researchers must first establish the right vaccine dose and patient safety before testing it further in high-risk women for triple-negative breast cancer. Other than race, a risk factor considered ill-defined, the predominant risk for developing one of these cancers has been linked to mutations in the most well-known breast cancer gene, BRCA1.
Tuohy hopes that once investigators finish the early phase of the trial, possibly by late summer, they can begin offering the vaccine to women who carry one of these genetic errors and face bilateral mastectomy to lower their risk. At present, this is the only preventive option now available to them.
Susan Jenks is a contributing writer.