New Immunotherapy Treatment Eliminates Stage IV Breast Cancer in Mice

Scientists at the Washington University School of Medicine in St. Louis identified a two-pronged approach using immune cells that eradicated metastasized breast cancer tumors in the rodent’s bones and kept cancer cells from returning.

Metastatic breast cancer — or stage IV breast cancer — occurs when cancer cells travel to other body parts, including the lungs, bones, brain, or liver. According to statistics, the metastatic disease eventually develops in nearly 30% of females diagnosed with early-stage breast cancer.

Treatments for metastatic breast cancer include chemotherapy, targeted therapies, hormonal therapy, or immunotherapy. In addition, oncologists may use surgery or radiation therapy to reduce the number of cancer cells.

Still, metastatic breast cancer can be challenging to treat effectively, and most treatments only slow the progression of the disease.

However, scientists from the Washington University School of Medicine in St. Louis may have found a new approach using supercharged immune cells to combat the disease.

Their research, published on March 8 in Cancer Discovery, found that when mice with metastatic breast cancer were given boosted immune cells called T cells and macrophages, they worked together to eliminate tumor cells in the rodent’s bones. Moreover, the immune cells continued to destroy cancer cells that attempted to return.

To conduct the study, the team treated mice with metastasized breast cancer in the bones with p38MAPK inhibitor and an immune therapy called OX40 agonist, which binds and engages T cells. They found that at least 80 days after receiving the treatment, all the rodents were free of cancer and alive. However, only half of the mice were alive 60 days after receiving one of the two treatments.

In a news release, senior author Sheila A. Stewart, Ph.D., the Gerty Cori Professor of Cell Biology & Physiology, says, "about 70% of patients with metastatic breast cancer have tumors that have spread to their bones. Our study suggests we may be able to use two treatments — one to sensitize the myeloid tumor microenvironment to immunotherapy, and one to activate T cells — to target these bone metastases in a way that eliminates the tumor, prevents the cancer from returning and protects against bone loss in the process."

After the combined treatment, Stewart says, "the mice look like they’re basically vaccinated against the cancer."

According to the study, "the combination of p38i, anti-OX40, and cytotoxic T cell engagement cured mice of metastatic disease and produced long-term immunologic memory."

In addition, the study’s findings lead researchers to question whether this two-pronged approach would effectively treat antigenic breast cancer.

Because of these promising results, the scientists hope to develop clinical trials using this immune cell combination in people with metastatic breast cancer that has spread to the bones.

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