Alloantibodies in the Treatment of Breast Cancer
Abstract
Cancerous cells use sophisticated strategies to avoid being recognized by the immune system. However, cancers cannot usually spread between individuals, suggesting that the immune system has the ability to recognize and kill tumor cells from other individuals. We discovered that most healthy people have antibodies (proteins made by immune cells that can recognize foreign molecules) that bind to tumors from other individuals, leading to their destruction by specialized immune blood cells. Healthy mice also have such tumor-binding antibodies, and by injecting these antibodies in combination with other immune-stimulating factors into mice with breast cancer, we were able to cure the tumors, including metastatic tumors that had spread from the breast to the lungs. Moreover, the treated mice showed only slight damage to normal tissues and had normal lifespans. We therefore believe that this strategy holds significant promise as a treatment and possible cure for breast cancer. In this project, we seek to address two overarching challenges related to this disease: revolutionize treatment regimens by replacing interventions that have life-threatening toxicities with ones that are safe and effective; and eliminate the mortality associated with metastatic breast cancer. However, to understand the clinical potential of this treatment, as well as its potential risks, we need to learn more precisely how it works. The treatment also needs to be tested in experimental animal models that more closely mimic human breast cancer in order to have a better idea of how safe and effective it would be in patients. In our proposed project, we will investigate the mechanism by which antibodies from healthy mice can recognize breast tumors and cause immune cells to attack them. In particular, we will identify the types of antibodies that bind tumors and pinpoint the molecules on tumor cells that the antibodies recognize. We will also evaluate the safety and effectiveness of our treatment strategy in experimental mouse models of metastatic breast cancer that are believed to simulate the human disease. This project should take approximately 3 years to complete. The information gained from these studies should allow us to design a mixture of human breast cancer-binding antibodies and immune stimulating factors that can be tested in a future clinical trial in patients with metastatic breast cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510037
Entities
People
- Edgar Engleman
Organizations
- Stanford University
- United States Army