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Weizmann Institute’s discovery blocks immune-suppressing “molecular bridges” in triple-negative breast cancer, showing potential to target multiple cancers
In a promising leap forward in cancer treatment, scientists from Israel’s Weizmann Institute of Science (WIS), alongside U.S. collaborators, have developed an antibody-based therapy that strengthens the body’s immune system to attack cancer cells more effectively, according to a recent statement by the WIS. This breakthrough could open new doors for treatment-resistant cancers, specifically targeting the tumor’s microenvironment rather than the tumor cells directly.
The Tumor’s Defense Mechanism: Molecular Bridges
The team’s research focused on a challenging cancer type—triple-negative breast cancer. Known for its aggressive nature and limited treatment options, this type of cancer has the ability to manipulate the body’s immune system to aid its own survival. The researchers found that triple-negative breast cancer cells create “molecular bridges” within the tumor’s microenvironment. These structures act as physical and biochemical barriers that shield the tumor from immune attacks by diverting nearby immune cells.
These bridges are composed of a protein called CD84, a molecule not commonly associated with breast cancer cells. While the cancer cells themselves produce CD84 in minimal amounts, they actively stimulate nearby immune cells to produce it, building bridges that suppress immune activity and allow the cancer to evade detection and destruction.
A Breakthrough Antibody Treatment
The WIS-led team developed an antibody treatment to counteract these bridges. By blocking CD84, the antibody disrupts the bridge-building process, freeing immune cells to mount a more aggressive attack on the tumor. In mouse models, this approach resulted in a dramatic reduction in tumor progression, even leading to full recovery in some cases.
The treatment protocol, administered twice weekly in mice, showcased the potential for halting and even reversing tumor growth. The researchers highlighted that this antibody targets cells with higher CD84 expression—primarily within the tumor—while sparing healthy immune cells, as these cells display CD84 in much lower levels. This precision targeting not only enhances the treatment’s effectiveness but also reduces potential side effects on healthy tissues.
CD84 Levels as a Prognostic Marker
The study also established a correlation between CD84 levels and patient outcomes. Higher CD84 levels in tumors were linked with shorter survival times, indicating that CD84 might serve as a predictive marker for the disease’s progression and treatment response. Additionally, experiments in genetically modified mice lacking CD84 revealed significantly smaller tumor growth, further confirming CD84’s role in dampening the immune response against cancer.
Implications for Broader Cancer Treatments
The researchers suggested that this treatment model could be applied beyond triple-negative breast cancer. By focusing on the tumor’s microenvironment rather than directly targeting cancer cells, the antibody could potentially benefit a wider range of cancer patients. This innovative approach moves away from the traditional strategy of targeting specific mutations in cancer cells, focusing instead on altering the immunosuppressive conditions within the tumor’s surroundings.
Dr. Michal Neeman, who led the research team, explained that the findings underscore the importance of immune modulation within the tumor microenvironment as a promising therapeutic strategy for hard-to-treat cancers. “Our aim is to equip the immune system with the necessary tools to dismantle the tumor’s defenses and enable it to perform its natural function—eliminating harmful cells,” she added.
Future Directions
While this antibody therapy is currently in the experimental stage, the study holds significant potential for future clinical applications. Researchers are optimistic about advancing to human trials to determine the antibody’s efficacy and safety profile in patients with triple-negative breast cancer and other types of cancer. If successful, this treatment could represent a critical step forward in immune-oncology, offering new hope for patients with cancers that resist existing therapies.
This study highlights a novel path forward in oncology, reflecting a growing understanding of cancer’s intricate interplay with the immune system and opening the door to therapies that could transform the landscape of cancer treatment worldwide.
