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Research at Mass General
The Immunobiology Laboratory performs basic, translational and clinical research investigating new therapeutic concepts to treat immune disorders ranging from autoimmune disease to cancer. Under the direction of Denise Faustman, MD, PhD, the laboratory is currently conducting the BCG Human Clinical Trial Program to investigate the BCG vaccine as a treatment for established type 1 diabetes.
Our basic research program is focused on uncovering the basic molecular and immunological mechanisms behind human and murine immune pathogenesis and translating these findings into new innovations in the clinic. One of our findings has been that boosting or restoring tumor necrosis factor (TNF) can selectively eliminate pathogenic T cells, induce beneficial regulatory T cells (Tregs) and induce organ regeneration, permanently curing mice of both type 1 diabetes and Sjögren’s-like syndrome. This basic science research has led to the establishment of clinical trial programs using repeat BCG vaccination in diverse human autoimmune diseases, including the BCG Human Clinical Trial Program being conducted at Massachusetts General Hospital.
Other basic science research in our lab is focused on the tumor necrosis factor receptor 2 (TNFR2) pathway. One of our fundamental basic science findings in the human is that the TNFR2 surface receptor is an identifying surface protein of the most potent Tregs, and that the TNFR2 pathway is an important signaling pathway for adult Treg fate. Based on these findings, our lab has been making and testing unique antibodies for TNFR2 with the goal of identifying antibodies that can lead to human Treg proliferation and depletion, which may have future applications in immunotherapy for both autoimmunity and cancer.
Our clinical research program is investigating whether repeat vaccination with a generic vaccine—called the bacillus Calmette-Guerin, or BCG, vaccine—can eliminate abnormal T cells, induce beneficial human regulatory T cells (Tregs) and reverse established type 1 diabetes in humans. Positive data from our Phase I study in humans were published in 2012. A Phase II trial is currently ongoing, as is a follow-up study to monitor the long-term effects of BCG vaccination in patients from the Phase I trial.
Most trials testing immune interventions in type 1 diabetes are conducted in new-onset diabetics. This clinical trial program is unique in focusing on patients with established, rather than newly diagnosed, type 1 diabetes. It is also unique in being a nonprofit drug development program (supported solely through philanthropic donations from the public and nonprofit organizations), as well as in seeking diabetes reversal using an inexpensive generic drug.
Learn more about the BCG Human Clinical Trial Program.
Denise Faustman, MD PhD, is Director of the Immunobiology Laboratory at Massachusetts General Hospital and an associate professor of medicine at Harvard Medical School. She has spent over two decades researching the nature of the molecular defect in T cells that results in the development of autoimmunity. Her current research focuses on discovering and developing new treatments for autoimmune diseases—with a focus on type 1 diabetes and Sjögren's syndrome—as well as other disorders of the immune system. Dr. Faustman is currently leading a human clinical trial program testing the efficacy of the BCG vaccine for reversal of established type 1 diabetes.
Dr. Faustman's type 1 diabetes research has earned her notable awards such as the Oprah Achievement Award for “Top Health Breakthrough by a Female Scientist” (2005), the "Women in Science Award" from the American Medical Women’s Association and Wyeth Pharmaceutical Company for her contributions to autoimmune disease research (2006), and the Goldman Philanthropic Partnerships/Partnership for Cures “George and Judith Goldman Angel Award” for research to find an effective treatment for type 1 diabetes (2011).
Her previous research accomplishments include the first scientific description of modifying donor tissue antigens to change their foreignness. This achievement earned her the prestigious National Institutes of Health and National Library of Medicine “Changing the Face of Medicine” Award (2003) as one of 300 American physicians (one of 35 in research) honored for seminal scientific achievements in the United States.
Summary of key research accomplishments:
Dr. Faustman earned her MD and PhD from Washington University School of Medicine in St. Louis, Missouri. After completing her internship, residency, and fellowships in Internal Medicine and Endocrinology at Mass General, Dr. Faustman became an independent investigator at Mass General and Harvard Medical School in 1987. She is a member of the American Association for the Advancement of Science (AAAS) and frequently serves in an advisory capacity to the Institute of Medicine of the National Academies in Washington, DC.
The Immunobiology Laboratory is focused on uncovering the basic molecular and immunological mechanisms behind human and murine immune pathogenesis and translating these new innovations to the clinic. The research explores mechanisms used by the immune system to allow the survival of autoimmune T cells, characterizing proteins in splenic stem cells from the mouse and the human that may contribute to pancreas regeneration after targeted T cell removal, identifying drugs that kill autoimmune T cells but not normal T cells, and investigating ways to promote or suppress regulatory T cells (Tregs) for applications in autoimmunity, oncology and infectious disease.
The BCG Human Clinical Trial Program is the culmination of over two decades of research at the Immunobiology Laboratory at Mass General. This program is focused on testing an inexpensive generic drug—bacillus Calmette-Guerin, or BCG—as a treatment for established type 1 diabetes. Our goal is to put longstanding type 1 diabetes into remission and prevent long-term diabetic complications. Results from our double-blind, placebo-controlled Phase I trial, published in 2012, showed that two doses of the BCG vaccine spaced four weeks aparthelped eliminate autoreactive T cells, temporarily restored the ability of the pancreas to produce small amounts of insulin, and induced beneficial regulatory T cells (Tregs) in adults who had been living with type 1 diabetes for an average of 15 years. A Phase II study was initiated in June 2015 and is ongoing. The Phase II trial is a double-blind, placebo controlled study that will test the efficacy of multiple doses of the BCG vaccine in 150 long-term diabetic subjects (average disease duration: 15-20 years; age: 18-65 years) with small, but detectable, levels of C-peptide secretion from the pancreas. The primary endpoint is a decrease in HbA1c in BCG treated vs placebo treated subjects. Patients will be followed for a total of five years.
More information about the BCG human clinical trial program:
View recent publications from the Immunobiology Lab at Mass General. Some full text publications may require a subscription
Diabetes Unit Immunobiology Laboratory
Contact our clinical trials coordinator to learn more about our research or schedule an appointment.Email Us Phone: 617-726-4084
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