This new antibody may stop one of the deadliest breast cancers

New research published in Breast Cancer Research highlights a potential new way to tackle this resistance. Scientists at MUSC Hollings Cancer Center developed an experimental antibody designed to interfere with multiple survival strategies used by TNBC cells. In early testing, the antibody slowed the growth of primary tumors, reduced the spread of cancer to the lungs, and revived immune cells that normally attack cancer. The treatment also killed cancer cells that no longer responded to chemotherapy.

Targeting a Key Cancer Enabler

The preclinical study centered on a protein called secreted frizzled-related protein 2 (SFRP2). This protein helps tumors thrive by encouraging the formation of new blood vessels, preventing cancer cells from dying, and weakening immune cells that would otherwise help eliminate the cancer.

The findings build on nearly 20 years of research led by Nancy Klauber-DeMore, M.D., a breast surgical oncologist who co-leads the Developmental Cancer Therapeutics Research Program at Hollings. The project involved a multidisciplinary team from MUSC's Surgery, Biochemistry and Molecular Biology, and Pathology and Laboratory Medicine departments.

"My lab first identified the role of SFRP2 in breast cancer in 2008," Klauber-DeMore said. "Since then, we've discovered its mechanism of action in breast cancer growth, metastasis and immune exhaustion and developed an antibody to block SFRP2."

The research team, which also included MUSC surgical resident Lillian Hsu, M.D., and former resident Julie Siegel, M.D., tested a humanized monoclonal antibody. This type of antibody is engineered to precisely attach to SFRP2 and block its cancer-promoting effects.

Reprogramming the Immune System Around the Tumor

To determine whether SFRP2 was a meaningful target in TNBC, the researchers first analyzed human tumor samples. They discovered that SFRP2 appeared not only in cancer cells but also in nearby immune cells, including tumor-infiltrating lymphocytes and macrophages.

"This is the first time anyone has demonstrated that SFRP2 is expressed on tumor-associated macrophages," Klauber-DeMore said. "That finding alone opens up an entirely new way of understanding and potentially manipulating the immune microenvironment."

Macrophages generally fall into two categories. M1 macrophages help activate the immune system to fight cancer, while M2 macrophages suppress immune activity and support tumor growth. In TNBC, macrophages tend to shift toward the M2 state. After treatment with the SFRP2 antibody, macrophages released large amounts of interferon-gamma, an immune signaling molecule that pushed them back toward the cancer-fighting M1 state.

Even in mice with advanced disease and existing metastases, the antibody improved the balance between M1 and M2 macrophages. This suggests the treatment may help retrain the immune system to respond to cancer at later stages.

"We discovered that it pushes macrophages toward the 'good' M1 state -- without the toxic effects you'd see if you gave interferon-gamma directly," Hsu said. "TNBC is so hard to treat, and so many therapies come with serious toxicities, so finding a way to activate the immune system without adding new side effects is especially meaningful."

The antibody also restored activity in T-cells, another critical part of the immune response. In TNBC, these cells often become exhausted and stop functioning properly. After antibody treatment, nearby T-cells became more active, indicating that the therapy could strengthen immune defenses that are typically weakened in cancer and potentially improve responses to immunotherapy.

Precision Targeting and Reduced Spread

In two different models of advanced TNBC, mice treated with the antibody developed significantly fewer lung tumors than untreated mice. Lung metastases indicate that cancer has entered the bloodstream and are linked to worse outcomes for patients.

The antibody's effectiveness was paired with a high level of precision. When researchers tracked where it traveled in the body, they found that it accumulated in tumor tissue but not in healthy organs or normal cells. This targeted behavior differs from traditional chemotherapy, which affects many types of cells and often causes serious side effects.

Overcoming Chemotherapy Resistance

The team also tested whether the antibody could address one of the biggest challenges in cancer care: resistance to chemotherapy. Doxorubicin, a commonly used drug for TNBC, often stops working over time as tumors adapt. When researchers created cancer cells that no longer responded to doxorubicin, the SFRP2 antibody still caused substantial cancer cell death.

"That's a very encouraging finding," Klauber-DeMore said, "because it suggests the therapy may be effective even when standard treatments fail."

A New Direction for Future Cancer Therapies

The study showed that SFRP2 is abundant throughout the tumor environment, appearing in cancer cells as well as surrounding immune cells such as tumor-infiltrating lymphocytes and tumor-associated macrophages. This widespread presence suggests that targeting SFRP2 could weaken tumors, boost immune activity, and bypass treatment resistance at the same time.

Importantly, SFRP2 did not build up in healthy blood or immune cells. This distinguishes the antibody from many immune-based therapies and supports its potential as a treatment that limits side effects while remaining effective.

By identifying SFRP2 as a central player linking tumor growth, immune suppression, and drug resistance, the research points to a new type of precision therapy that could complement or strengthen existing immunotherapies for TNBC.

"Our hope," Klauber-DeMore said, "is that this will one day offer patients a new option -- one that not only treats the cancer but also re-engineers the immune system's ability to fight it."

While additional studies are required, the early results are encouraging. The antibody has been licensed to Innova Therapeutics, a Charleston-based biotechnology company co-founded by Klauber-DeMore, which is working to secure funding for a first-in-human clinical trial. The therapy has also received Rare Pediatric Disease and Orphan Disease designations from the Food and Drug Administration (FDA) for osteosarcoma, another cancer strongly linked to SFRP2. These designations do not allow patient use yet but provide incentives to support continued development.

"The preliminary data are really encouraging," Hsu said. "I feel grateful to have been part of research that could one day help so many patients."