A groundbreaking experimental antibody may offer a powerful new weapon against triple-negative breast cancer (TNBC), one of the most aggressive and challenging forms of the disease. Developed by scientists at the Medical University of South Carolina (MUSC) Hollings Cancer Center, this treatment targets a critical protein that fuels tumor growth and suppresses the body’s immune defenses, effectively re-engaging the immune system against cancer, as reported by ScienceDaily.com.
TNBC is notoriously difficult to treat because it lacks the hormone receptors that allow other breast cancers to respond to targeted therapies. It grows rapidly, spreads aggressively, and frequently returns with increased resistance after initial treatments. This urgent need for new solutions underscores the significance of the recent findings.
The findings detail how the antibody can interfere with multiple survival strategies employed by TNBC cells. Published in the journal Breast Cancer Research, the preclinical study highlights the antibody’s ability to slow primary tumor growth, reduce lung metastases, and even destroy chemotherapy-resistant cancer cells.
Targeting SFRP2: A key enabler of cancer
The research centers on a protein known as secreted frizzled-related protein 2 (SFRP2), identified by Dr. Nancy Klauber-DeMore, a breast surgical oncologist and co-leader of the Developmental Cancer Therapeutics Research Program at Hollings. Her lab first pinpointed SFRP2’s role in breast cancer back in 2008.
Subsequent work elucidated its mechanisms in tumor growth, metastasis, and immune exhaustion. SFRP2 acts as a central player in helping tumors thrive by promoting the formation of new blood vessels, preventing cancer cells from undergoing natural death, and crucially, weakening the immune cells that would otherwise attack the cancer.
The newly developed humanized monoclonal antibody is engineered to precisely bind to and block these cancer-promoting effects of SFRP2. This precision targeting offers a promising avenue for a new antibody breast cancer treatment.
Reprogramming the immune system to fight TNBC
A pivotal discovery revealed SFRP2’s presence not only in cancer cells but also in nearby immune cells, particularly tumor-infiltrating lymphocytes and macrophages. This finding, “the first time anyone has demonstrated that SFRP2 is expressed on tumor-associated macrophages,” as Dr. Klauber-DeMore noted, opens new avenues for manipulating the immune microenvironment.
Macrophages typically exist in two states: M1, which activates the immune system to fight cancer, and M2, which suppresses immunity and supports tumor growth. In TNBC, macrophages often shift towards the M2 state. However, treatment with the SFRP2 antibody prompted macrophages to release interferon-gamma, pushing them back towards the cancer-fighting M1 state.
This rebalancing of macrophage types occurred even in mice with advanced disease and existing metastases, suggesting the treatment could retrain the immune system at later stages. Lillian Hsu, M.D., an MUSC surgical resident involved in the study, emphasized the significance: “We discovered that it pushes macrophages toward the ‘good’ M1 state – without the toxic effects you’d see if you gave interferon-gamma directly.”
Beyond macrophages, the antibody also revitalized T-cells, another crucial component of the immune response often exhausted in TNBC. Treated T-cells became more active, indicating the therapy could strengthen the body’s natural defenses and potentially enhance responses to existing immunotherapies. In preclinical models, mice receiving the antibody showed significantly fewer lung tumors.
The development of this new antibody represents a significant leap forward in the quest to combat triple-negative breast cancer. By simultaneously attacking tumor growth and reinvigorating the immune system, it offers a dual-action approach with reduced toxicity compared to direct immune stimulants.
While further clinical trials are essential, these early results provide compelling evidence for a future where TNBC might be more effectively managed, transforming patient outcomes through a novel new antibody breast cancer therapy.
