Combination Immunotherapy on Solid Tumors
Tanya Mayadas, PhD, senior scientist at Brigham and Women’s Hospital, is the principal investigator at the Mayadas Lab. Her team is exploring an innovative approach that combines neutrophils with immunotherapy to treat solid tumors. Immunotherapy is a cutting-edge type of cancer treatment that uses the body’s immune system to target and destroy cancer cells, offering new hope for more effective and durable (or lasting) treatments.
What are neutrophils?
Dr. Mayadas: Neutrophils are the most common type of white blood cell in our blood, generated in the billions every day. They are critical for defending against bacterial and viral infections. However, in the context of cancer, neutrophils have a bad reputation because their accumulation within tumors is often associated with tumor growth and poor prognosis.
How can neutrophils help patients fight cancer?
Dr. Mayadas: Neutrophils, which are plentiful in the body, can be transformed into cancer-fighting cells. We target them with an intravenously (IV) delivered antibody-based biologic that enables neutrophils to educate and mature T-cells. These T-cells then perform all the critical anti-tumor responses. This process expands and activates cancer-fighting T-cells, drives T-cell infiltration into the tumor, and generates memory T-cells. Together, these actions enhance the body’s ability to durably fight cancer.
What are Memory T-cells and why are they important?
Dr. Mayadas: Memory T-cells remember the tumor and act as our body’s surveillance system. They identify and eradicate the tumor if it re-emerges, even before we are aware of the tumor’s recurrence. This ability to "remember" is important for long-term cancer prevention and treatment.
How do T-cells attack solid tumors?
Dr. Mayadas: Cancer-killing T-cells can eliminate tumors directly, but they must penetrate deep into the tumor to be effective. Some solid tumors have an immunosuppressive tumor microenvironment that makes it challenging for T-cells to infiltrate the tumor. This limits the impact of FDA-approved T-cell-focused immunotherapies, such as immune check-point inhibitors that remove the brakes on all T-cells, and chimeric-antigen receptor T-cells (CAR-T) genetically engineered to directly attack the tumor. T-cells that are educated by neutrophils targeted with our antibody-based biologic acquire the ability to both infiltrate the tumor and kill the tumor cells. Therefore, our biologic, alone or in combination with FDA approved immunotherapies, could achieve effective and long-lasting tumor eradication.
What’s the future of this type of treatment?
Dr. Mayadas: Cancer continues to rank as the second leading cause of death globally, following cardiovascular disease. Therefore, there is an urgent need for approaches that lead to effective and lasting anti-tumor responses. Compared with other options, immunotherapies offer significant advantages because they instruct your own immune system on how to fight the tumor. This is a very exciting area for me, as it continues to unveil novel pathways that may be targeted for anti-tumor therapy. As a researcher passionate about translational science, it would be tremendously gratifying if my life’s work studying neutrophils in the immune system results in a potential immunotherapy for cancer.
