Zhen Fan, MD

Developing novel approaches to treat and prevent metastasis in HER2-positive breast cancer.

Impact

Once breast cancer spreads to other tissues in the body—a process called metastasis—it has become resistant to many therapies and is incurable. Lack of response to current standard-of- care, including novel targeted cancer therapy, is the primary cause of deaths from breast cancer. While immunotherapy is reshaping current cancer treatment paradigms, a weak immune response in breast cancer hampers the use of it to treat this disease. To address this challenge, Dr. Fan is investigating a way to prompt the body’s natural immunity to launch an immune response to destroy cancer by “tricking” it into perceiving breast cancer cells as influenza virus-infected cells. If successful, this strategy may lead to a breakthrough in treatment and prevention of breast cancer recurrence and metastasis.

Progress Thus Far

Dr. Fan has developed a drug delivery system that works by delivering flu protein antigens to breast cancer cells to activate an immune response. He successfully showed in breast cancer models that tagging metastatic breast cancer with these flu biomarkers tricks the immune system into attacking them. To deliver the flu proteins, Dr. Fan and his team are testing tiny nanoparticles called exosomes. The team demonstrated the efficiency of HER2-targeting exosomes in targeting and entering HER2-positive tumor cells where the release of a viral antigen significantly inhibited tumor growth.

What’s next

In the coming year, Dr. Fan and his team will work to optimize the exosome delivery system using a patient’s own immune cells to produce tumor-targeting exosomes. These “living drugs” will be designed not only to deliver viral antigens directly to tumors, but also to release signals that draw cancer-fighting T cells into the tumor. This innovative approach could inform a new type of cancer immunotherapy.