New vaccine shows potential in preventing recurrence of triple-negative breast cancer

A small clinical trial shows promising results for patients with triple-negative breast cancer who received an investigational vaccine designed to prevent recurrence of tumors. Conducted at Washington University School of Medicine in St. Louis with a therapy designed by WashU Medicine researchers, the trial is the first to report results for this type of vaccine -; known as a neoantigen DNA vaccine -; for breast cancer patients.

The study, which found the vaccine to be well-tolerated and to stimulate the immune system, is available Nov. 14 in the journal Genome Medicine.

Following treatment, 14 of 18 patients showed immune responses to the vaccine and, after three years, 16 patients remained cancer-free. While the early-stage trial was designed to evaluate safety of the vaccine and did not include a control group to determine efficacy, the researchers analyzed historical data from patients with triple-negative breast cancer treated with the standard of care only. In that group, on average, about half of patients remained cancer-free at three years post-treatment.

Triple-negative breast cancer is an aggressive tumor type that grows even in the absence of the hormonal fuel that drives growth of other types of breast cancer. To date, triple-negative breast cancer has no targeted therapies and is usually treated with traditional approaches that include surgery, chemotherapy and radiation therapy. For reasons that scientists are still investigating, this tumor tends to be more common among African American patients diagnosed with breast cancer. In this trial, one-third of the participants (six of 18) were African American.

For this trial, patients with triple-negative breast cancer who still had evidence of a tumor remaining after a first round of chemotherapy were eligible to participate. Such patients are at high risk of cancer recurrence even after the remaining tumor is surgically removed. After surgical removal, the research team analyzed and compared the tumor tissue with the same patient's healthy tissue to find unique genetic mutations in the cancer cells. Such mutations in a patient's cancer cells alter the proteins only in the tumor, making it possible to train the immune system to go after the altered proteins and leave healthy tissues alone.

Using software they designed, the researchers selected altered proteins -; called neoantigens -; that were made by the patients' tumors and that were identified as most likely to trigger a strong immune response. On average, each patient's vaccine contained 11 neoantigens (ranging from a minimum of four to a maximum of 20) specific to their tumor.

Several studies of cancer vaccines are ongoing at Siteman. Vaccines for all of these trials are made in a WashU Medicine facility that meets the good manufacturing practice (GMP) requirements set by the Food and Drug Administration. In some of the vaccine clinical trials for breast cancer patients, personalized vaccines are being investigated in combination with immunotherapies called checkpoint inhibitors that boost the action of T cells.

"We are excited about the promise of these neoantigen vaccines," Gillanders said. "We are hopeful that we will be able to bring more and more of this type of vaccine technology to our patients and help improve treatment outcomes in patients with aggressive cancers."

Zhang X, Goedegebuure P, Chen MY, Mishra R, Zhang F, Yu YY, Singhal K, Li L, Gao F, Myers NB, Vickery T, Hundal J, McLellan MD, Sturmoski MA, Kim SW, Chen I, Davidson JT, Sankpal NV, Myles S, Suresh R, Ma CX, Foluso A, Wang-Gillam A, Davies S, Hagemann IS, Mardis ER, Griffith O, Griffith M, Miller CA, Hansen TH, Fleming TP, Schreiber RD, Gillanders WE. Neoantigen DNA vaccines are safe, feasible, and induce neoantigen-specific immune responses in triple-negative breast cancer patients. Genome Medicine. Nov. 14, 2024.

This work was supported by Susan G. Komen for the Cure, grant number KG111025; the Alvin J. Siteman Cancer Center/Siteman Investment Program grant 4035; the National Institutes of Health (NIH), grant numbers R01 CA240983, P30‐CA091842, U01 CA248235 and T32 CA009621; the Foundation for Barnes‐Jewish Hospital; and the Centene Corporation contract P19‐00559 B101 for the Washington University‐Centene ARCH Personalized Medicine Initiative.

Xia H, Hoang MH, Schmidt E, Kiwala S, McMichael J, Skidmore ZL, Fisk B, Song JJ, Hundal J, Mooney T, Walker JR, Goedegebuure SP, Miller CA, Gillanders WE, Griffith OL, Griffith M. pVACview: an interactive visualization tool for efficient neoantigen prioritization and selection. Genome Medicine. Nov. 14, 2024.

This work was supported by the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH), grant number R00HG007940; the National Cancer Institute (NCI) of the NIH, grant number U01CA248235; the V Foundation for Cancer Research, award number V2018-007; the Centene Corporation contract P19-00559 for the Washington University-Centene ARCH Personalized Medicine Initiative; and the Goldberg Family Foundation.

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Washington University School of Medicine

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