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December 8, 2025
CHARLESTON, S.C. — In a significant development for the treatment of one of the deadliest forms of breast cancer, researchers have identified a novel antibody therapy that halts the progression of triple-negative breast cancer (TNBC) in preclinical models. The study, conducted by a team at the Medical University of South Carolina (MUSC) Hollings Cancer Center, reveals a new method to “retrain” the immune system to attack cancer cells, potentially overcoming the drug resistance that plagues current standard treatments.
The findings, published this week, offer renewed hope for patients facing TNBC, a subtype that lacks the three most common receptors known to fuel breast cancer growth—estrogen, progesterone, and HER2. Consequently, it does not respond to hormonal therapies or HER2-targeted drugs, often leaving chemotherapy as the primary, yet frequently insufficient, line of defense.
The Breakthrough: Targeting the “Cancer Enabler”
The research team, led by Dr. Nancy Klauber-DeMore, a breast surgical oncologist, and Dr. Lillian Hsu, a surgical resident, focused on a specific protein called secreted frizzled-related protein 2 (SFRP2). While previously known to play a role in tumor development, the new study identifies SFRP2 as a critical “cancer enabler” that not only fuels tumor growth and blood vessel formation but also actively suppresses the immune system’s ability to fight the disease.
“My lab first identified the role of SFRP2 in breast cancer in 2008,” said Dr. Klauber-DeMore in a statement. “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 team developed a humanized monoclonal antibody designed to bind to SFRP2 and neutralize its effects. In laboratory tests involving models of advanced TNBC, the antibody successfully suppressed primary tumor growth and significantly reduced the spread of cancer to the lungs—a common and often fatal site of metastasis.
Flipping the Immune Switch
One of the study’s most critical discoveries is how the antibody alters the tumor microenvironment. Tumors are often surrounded by macrophages, a type of white blood cell. In cancer, these cells typically exist in an “M2” state, which suppresses the immune system and helps the tumor grow.
The researchers found that the new antibody causes these macrophages to release a surge of interferon-gamma, a signaling protein that flips them into an “M1” state—the “warrior” mode that attacks cancer cells.
“This is the first time anyone has demonstrated that SFRP2 is expressed on tumor-associated macrophages,” Dr. Klauber-DeMore noted. “That finding alone opens up an entirely new way of understanding and potentially manipulating the immune microenvironment.”
This “reprogramming” effect also re-energized T-cells, the immune system’s primary soldiers, which often become exhausted in the presence of aggressive tumors.
Overcoming Chemotherapy Resistance
Perhaps most significantly for patients with recurring disease, the antibody proved effective against cancer cells that had stopped responding to doxorubicin, a standard chemotherapy drug for TNBC. Resistance to chemotherapy is a major hurdle in treating advanced breast cancer; once a tumor becomes resistant, treatment options dwindle rapidly.
“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,” said Dr. Hsu.
Expert Perspectives and Implications
The oncology community has welcomed the findings as a crucial step toward “precision immunotherapy.” While current immunotherapies like checkpoint inhibitors work for some TNBC patients, they rely on the tumor already being “hot” (visible to the immune system). This new antibody appears capable of turning “cold” tumors “hot.”
Dr. Simon Vincent, Director of Research, Support and Influencing at Breast Cancer Now, who was not involved in this specific study, has emphasized the urgency of such breakthroughs for this patient demographic. “We know how urgently these women need new treatment options,” Vincent noted in relation to recent advancements in the field. “This form of the disease can be more challenging to treat, may be more likely to return or spread in the first few years following treatment, and it affects younger women and Black women more than other groups.”
Independent experts suggest that if these preclinical results translate to human trials, the SFRP2 antibody could be used in combination with existing immunotherapies to enhance their effectiveness or as a second-line option when chemotherapy fails.
Limitations and Next Steps
While the results are promising, the therapy is currently in the preclinical stage, meaning it has been tested in cell lines and animal models but not yet in humans. The timeline for clinical trials is expected to be the next major hurdle, as safety and dosage profiles must be rigorously established.
Additionally, researchers must determine if the antibody is effective across all genetic variations of TNBC or if it is best suited for a specific subset of patients with high SFRP2 expression.
Despite these necessary caveats, the discovery represents a tangible pivot from “bombarding” the body with toxic chemotherapy to “engineering” the body’s own defenses to recognize and destroy the malignancy.
Medical Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.
References
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Primary Study: Hsu, L., Siegel, J., et al. (2025). “Antibody targeting SFRP2 reprograms macrophages and halts triple-negative breast cancer progression.” Breast Cancer Research.
