Researchers at the MUSC Hollings Cancer Center have developed a new antibody that may offer hope for patients with triple-negative breast cancer (TNBC), one of the most aggressive and difficult-to-treat forms of breast cancer. TNBC is known for its rapid growth, early spread, and lack of hormone receptors, which makes it resistant to many targeted therapies. Even when initial treatments are effective, the cancer often returns in a more resistant form.
The study, published in Breast Cancer Research, details how the newly developed antibody blocks several mechanisms that allow TNBC cells to survive, grow, and evade the immune system. In preclinical tests, this antibody was shown to suppress primary tumor growth and reduce the spread of cancer to the lungs. It also reactivated immune cells responsible for fighting cancer and killed cancer cells that had become resistant to chemotherapy.
The research focused on secreted frizzled-related protein 2 (SFRP2), a protein that supports tumor growth by aiding blood vessel formation, preventing cell death, and weakening immune responses against tumors. The project builds on nearly 20 years of work on SFRP2 by Nancy Klauber-DeMore, M.D., a breast surgical oncologist who co-leads Hollings' Developmental Cancer Therapeutics Research Program. The team included experts from various departments at MUSC.
To test whether SFRP2 could be an effective target for TNBC treatment, researchers examined human triple-negative breast tumors and found SFRP2 present not only in tumor cells but also in nearby immune cells such as tumor-infiltrating lymphocytes and macrophages.
"This is the first time anyone has demonstrated that SFRP2 is expressed on tumor-associated macrophages," said Klauber-DeMore. "That finding alone opens up an entirely new way of understanding and potentially manipulating the immune microenvironment."
Macrophages are immune cells that can either help fight cancer (M1 type) or support its growth (M2 type). In TNBC cases, they typically lean toward the M2 type. However, after treatment with the SFRP2 antibody, these macrophages released interferon-gamma—a signal that shifted them toward the M1 state associated with anti-cancer activity—even in mice whose cancer had already spread.
"We discovered that it pushes macrophages toward the 'good' M1 state – without the toxic effects you'd see if you gave interferon-gamma directly," said Lillian Hsu, M.D., one of the study's lead researchers. "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 helped reinvigorate T-cells—another group of immune cells—that often become exhausted during TNBC progression. After exposure to the antibody, these T-cells became more active.
In advanced disease models using mice with TNBC metastasis to their lungs—a sign of particularly poor prognosis—the antibody significantly reduced lung tumors compared to untreated animals.
Importantly, when researchers tracked where the antibody traveled in animal bodies, they found it concentrated specifically in tumor tissue rather than healthy organs or normal growing cells. This selectivity could help avoid some common side effects seen with traditional chemotherapies.
The team also tested whether this approach could overcome resistance to doxorubicin—a standard chemotherapy drug for TNBC—to which many tumors eventually stop responding. They created doxorubicin-resistant cancer cells and found that treatment with their antibody still led to strong cell death among these otherwise hard-to-treat cells.
"That's a very encouraging finding," said Klauber-DeMore. "because it suggests the therapy may be effective even when standard treatments fail."
High levels of SFRP2 were detected throughout both tumor tissue and surrounding immune environments—suggesting this single-targeted therapy might simultaneously weaken tumors while strengthening patient immunity against them.
Another notable result was that SFRP2 did not accumulate in healthy blood or immune cells—a contrast from other immunotherapies—which could mean fewer unwanted side effects if translated into clinical use.
By identifying SFRP2’s role at key points between tumor growth promotion and suppression of immunity or treatment resistance—the study sets groundwork for future precision therapies potentially used alongside existing immunotherapies for TNBC patients.
"Our hope," said Klauber-DeMore,"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."
Although further studies are needed before human trials can begin—early results show promise. The antibody has been licensed by Innova Therapeutics—a Charleston-based biotechnology company co-founded by Klauber-DeMore—which plans fundraising efforts for first-in-human clinical trials. Additionally,the U.S.Food & Drug Administration has granted Rare Pediatric Disease & Orphan Disease designations for osteosarcoma—another condition linked closely with SFRP2—but these designations do not yet permit patient use; instead they provide incentives supporting continued drug development as clinical testing advances.
"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."
