In a recent study titled “Safety and preliminary evidence of biological efficacy of a mammaglobin-A DNA vaccine in patients with stable metastatic breast cancer”, and published in the Clinical Cancer Research journal, a team of researchers from Washington University School of Medicine, St. Louis, evaluated the safety and biological efficacy of a breast cancer vaccine in patients suffering with the metastatic form of the disease.
The results indicated this vaccine was able to activate the patient’s immune system, allowing it to attack cancer cells and therefore slower tumor progression.
Researchers found that a protein called Mammaglobin-A (MAM-A) is expressed at high levels in 40% to 80% of primary breast cancers. As such, the new vaccine (MAM-A DNA) directs the patient’s immune system to target this protein, which is almost exclusive to breast cancer cells.
“Being able to target mammaglobin is exciting because it is expressed broadly in up to 80 percent of breast cancers, but not at meaningful levels in other tissues,” senior author William E. Gillanders, MD, professor of surgery said in a news release. “In theory, this means we could treat a large number of breast cancer patients with potentially fewer side effects. It’s also exciting to see this work progress from identifying the importance of mammaglobin-A, to designing a therapeutic agent, manufacturing it and giving it to patients, all by investigators at Washington University,” he added.
In this Phase I clinical trial, 14 patients with stable metastatic breast cancer expressing mammaglobin-A were enrolled in the study. Immune responses elicited by the vaccine (CD8 T cell levels) were measuredby ELISPOT, flow cytometry, and cytotoxicity assays.
Some patients demonstrated some side effects, including rash, tenderness at the vaccination site and mild flu-like symptoms. However, no serious or life-threatening effects were observed.
The results showed that there was a significant increase in the levels of MAM-A–specific CD8 T cells after vaccination, along with an increase in MAM-A–specific IFNγ-secreting T cells. Furthermore, even though the trial was not specifically designed to assess progression-free survival (PFS), initial evidence suggested that vaccinated subjects had an improved PFS when compared to those who did not receive the vaccine.
“Despite the weakened immune systems in these patients, we did observe a biologic response to the vaccine while analyzing immune cells in their blood samples,” Dr.Gillanders explained. “That’s very encouraging. We also saw preliminary evidence of improved outcome, with modestly longer progression-free survival.”
Due to the promising results of this study, the team is planning to develop a bigger clinical trial to evaluate the efficacy of the vaccine in newly diagnosed breast cancer patients, who have healthier immune systems than patients who already underwent aggressive cancer treatments.
“If we give the vaccine to patients at the beginning of treatment, the immune systems should not be compromised like in patients with metastatic disease,” Dr. Gillanders said. “We also will be able to do more informative immune monitoring than we did in this preliminary trial. Now that we have good evidence that the vaccine is safe, we think testing it in newly diagnosed patients will give us a better idea of the effectiveness of the therapy.”