New vaccine shows potential to prevent recurrence of triple-negative breast cancer

A small clinical trial has shown promising results for triple-negative breast cancer patients who received an investigational vaccine designed to prevent tumor recurrence. The trial, conducted at Washington University School of Medicine in St. Louis using a treatment designed by WashU Medicine researchers, is the first to report results for this type of vaccine. Also known as neoantigen DNA vaccine – for breast cancer patients.

The study, which found the vaccine was well-tolerated and stimulated the immune system, will be published in the journal Genome Medicine on November 14.

Phase I clinical trial – conducted at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine – The study included patients diagnosed with triple-negative breast cancer that is non-metastatic and has not spread to other organs. Eighteen patients participated. Each patient receives standard treatment and three doses of a personalized vaccine tailored to identify key mutations in their specific tumor and train immune cells to recognize and attack cells with these mutations. received the dose.

After treatment, 14 of 18 patients developed an immune response to the vaccine, and 16 patients remained cancer-free three years later. The early-stage trial was designed to assess the safety of the vaccine and did not include a control group to determine safety. efficacyResearchers analyzed historical data from triple-negative breast cancer patients treated with standard therapy alone. In that group, on average, about half of the patients remained cancer-free three years after treatment.

“These results were better than we expected,” said lead author William E. Gillanders, MD, Mary Culver Distinguished Professor of Surgery at WashU Medicine, who treats patients at Siteman. said. “Obviously, this is not a perfect comparison and we recognize the limitations of this type of analysis, but we continue to pursue this vaccine strategy and will continue to pursue randomized controlled trials that directly compare the vaccine to standard care.” “We are encouraged by what we are seeing in these patients so far compared to standard treatment alone.”

Triple-negative breast cancer is an aggressive tumor type that grows even in the absence of the hormonal fuel that fuels the growth of other types of breast cancer. To date, triple-negative breast cancer has no targeted therapy and is usually treated with traditional approaches such as surgery, chemotherapy, and radiation therapy. This tumor tends to be more common among African-American patients, for reasons that scientists are still investigating. diagnosed with breast cancer. In this study, one-third of the participants (6 of 18) were African American.

The trial was open to triple-negative breast cancer patients with evidence of residual tumor after initial chemotherapy. These patients are at high risk for their cancer to come back even after the remaining tumor is surgically removed. After surgical removal, the research team analyzed the tumor tissue and compared it with healthy tissue from the same patient, finding unique genetic mutations within the cancer cells. These mutations in a patient's cancer cells change only the proteins within the tumor, allowing the immune system to track the altered proteins and train it to leave healthy tissue alone.

The researchers used software they designed to select the modified proteins. Called neoantigens – they are produced by a patient's tumor and identified as most likely to cause a strong immune response. On average, each patient's vaccine contained 11 neoantigens (ranging from a minimum of 4 to a maximum of 20) specific to that tumor.

Software development was led by computational biologists Obi Griffiths, Ph.D., professor of medicine, and Malachi Griffiths, Ph.D., associate professor of medicine, in WashU Medicine's Department of Oncology. A related paper published simultaneously in the same journal describes the software tools they developed. One of their goals is to make these computational resources widely accessible to cancer researchers and clinicians around the world.

We hope to promote the use of this software in cancer vaccine design. These are complex algorithms, but in general the software takes a list of mutations and interprets them in terms of their potential to be good neoantigen candidates. This tool ranks possible neoantigens based on current knowledge about what is important in stimulating the immune system to attack cancer cells. These software tools were developed with support from the National Cancer Institute and have open licenses that make them widely available for both academic and commercial use. ”

Dr. Malachi Griffiths, Associate Professor of Oncology, WashU Medicine

Several cancer vaccine studies are underway at Siteman. The vaccines in all of these trials are manufactured at WashU Medicine facilities that meet Good Manufacturing Practice (GMP) requirements set by the Food and Drug Administration. Some vaccine trials for breast cancer patients are investigating personalized vaccines in combination with immunotherapies called checkpoint inhibitors, which boost T-cell activity.

“We are excited about the promise of these neoantigen vaccines,” Gillanders said. “We look forward to making this type of vaccine technology increasingly available to patients and contributing to improved outcomes for 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. , Sankupal NV, Miles S, Suresh R, Ma CX, Forso A, Wangiram A, Davis S, Hageman IS, Mardis ER, Griffiths O, Griffiths 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. Genomic medicine. November 14, 2024.

This research was supported by Susan G. Komen for the Cure (grant number KG111025). Alvin J. Siteman Cancer Center/Siteman Investment Program Grant 4035. National Institutes of Health (NIH), grant numbers R01 CA240983, P30-CA091842, U01 CA248235 and T32 CA009621. Barnes-Jewish Hospital Foundation. and Centene Corporation have entered into Agreement P19-00559 B101 for the University of Washington-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. Genomic medicine. November 14, 2024.

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