Israeli Scientists Develop Antibody to Combat Aggressive Breast Cancer

A new study led by Professor Idit Shahar at the Weizmann Institute of Science reveals that aggressive breast cancer cells in the body create “molecular bridges” to weaken the immune system’s response. This research, recently published in Cell Reports, found that these bridges suppress the immune system’s natural defenses, allowing cancer cells to thrive undisturbed. However, a newly developed antibody has shown promise in blocking these bridges, enabling the immune system to resume its attack on cancer cells.

The Science Behind "Molecular Bridges" and Immune Suppression

The concept of “molecular bridges” borrows from the strategic advice of Sun Tzu, allowing cancer cells to "build a retreat" for immune cells, thereby diverting attacks. Professor Shahar’s team discovered that aggressive breast cancer cells induce immune cells in their environment to express the protein CD84, which creates connections between cells, forming these immune-suppressing bridges.

"CD84 helps cancer develop by allowing immune-suppressing cells to gather around the tumor and prevent a direct immune attack," Shahar explained. In the study, mice genetically modified to lack the CD84 protein showed significantly slower tumor growth, while treatment with an antibody blocking these bridges even led to complete cancer remission in some cases.

Implications for Treating Triple-Negative Breast Cancer (TNBC)

Shahar’s research focused on triple-negative breast cancer (TNBC), the most aggressive and difficult-to-treat form of breast cancer, often associated with mutations in BRCA1 and BRCA2 genes. Unlike other cancer types, TNBC cells lack unique surface markers, making them resistant to conventional targeted therapies. This discovery opens a new therapeutic pathway by targeting the tumor’s microenvironment rather than the cancer cells themselves.

The Weizmann Institute team partnered with the City of Hope Cancer Research Center in California to analyze samples from TNBC patients. They found that while breast cancer cells express low levels of CD84, the tumor microenvironment exhibited high CD84 activity, leading to immune suppression. Patients with elevated CD84 levels in their tumors generally had poorer survival rates.

Expanding the Research to Broader Applications

Researchers are hopeful that this antibody treatment could be adapted for other cancers where immune suppression plays a role. The team also identified regulatory B cells as key players in immune suppression within the tumor’s microenvironment. Blocking CD84 could prevent these cells from releasing immune-suppressing proteins that disable T cells, which are crucial for attacking cancer cells.

Moving Toward Personalized Cancer Therapies

Shahar highlighted that the antibody specifically targets the tumor environment, minimizing potential side effects on healthy cells. "In the era of personalized medicine, we present a therapeutic approach that targets the tumor’s microenvironment and not the cancer cells directly, potentially making this therapy suitable for a wide range of patients," she explained.

Conclusion and Future Directions

This study offers a promising step forward in cancer treatment, particularly for patients with aggressive cancers like TNBC that lack effective therapies. With ongoing research and potential human trials on the horizon, the Weizmann Institute’s findings could pave the way for a new approach in immunotherapy, one that enhances the body's natural defenses by dismantling cancer’s molecular defenses.

Participating in the study were researchers from the City of Hope Cancer Research Center, along with Prof. Amin Gulsen Gunes, Dr. Martin Jones, Dr. Emin Lee, and Prof. Raju Pillai. The collaborative effort between Israeli and U.S. scientists underscores the global importance of advancing cancer research and offering hope for more effective treatments.