Robert S. Mittler - Department of Surgery - Emory University

INVITED SPEAKER:
1990 New York Medical College, Department of Microbiology and Immunology, Valhalla NY
1993 Seattle Biomedical Research Institute, Seattle, WA
1994 Robert W. Franz Cancer Research Center, Earle A Chiles Research Institute, Providence
Portland Medical Center, Portland, OR
1997 Cambridge University, Conference on Mucins and Tumor Immunology, Cambridge,
England
1999 Oregon State University, Department of Microbiology and Immunology, Corvallis, OR
2001 Leiden University Health Sciences Center, Department of Hematology and Tumor
Immunology
2001 Northwest Research Institute, Department of Immunology, Seattle, WA
2002 University of Seoul, Fourth Annual Immunology Meeting, Seoul, South Korea
2002 Ulsan University, Department of Immunology, Ulsan, South Korea
2003 Memorial Sloan-Kettering Cancer Center, New York, NY
2003 Cornell University School of Medicine, New York, NY
2003 University of Connecticut Health Sciences Center, Department of Immunology,
Farmington, CT.
2005 Crossroads between Innate and Adaptive Immunity Conference, Rhodes, Greece.
2005 H. Lee Moffitt Cancer Center, University of South Florida.
2005 American Congress Of Rheumatology – Annual Meeting, San Diego CA.
2006 Symposium for Cell and Gene Therapy, Martin Luther University Hospital, Halle-
Wittenburg, Germany.
2006 La Jolla Institute for Allergy and Immunology, San Diego CA.
2008 University of Miami School of Medicine, Miami, FL.
2008 University of Ulsan, Ulsan, South Korea
2008 The NIH Rocky Mountain National Laboratory
RESEARCH FOCUS:
Our research interests center on the CD137 (TNFRSF9 – 4-1BB) T cell costimulatory receptor,
a member of the TNFR superfamily and how it functions in regulating the immune system - with
emphasis on enhancing the induction of anti-viral and anti-tumor immunity, and the suppression
of autoimmunity. CD137 receptors are activation-induced on T cells, NK cells, NKT cells,
granulocytes, macrophages and dendritic cells. CD137 is constitutively expressed on
neutrophils, and in humans it can be expressed on neurons, astrocytes and microglia. On T
cells CD137 can serve as a costimulatory receptor, the crosslinking of which upregulates antiapoptotic
survival signals. The ligand for CD137, 4-1BBL, a member of the TNF superfamily is
weakly expressed on B cells but is upregulated upon B cell activation. Its expression is also
upregulated on other professional antigen-presenting cells (APCs) after activation or
maturation. We have found that although CD137 is expressed on activated CD4 and CD8
positive T cells, anti-CD137 mediated signaling preferentially upregulates CD8 + T cell function
and survival in vitro and in vivo. We have also found that CD137 ligands induce the eradication
of established poorly immunogenic tumors and reverse established autoimmune diseases such
as rheumatoid arthritis and systemic lupus erythematosis. Recently we have found that the
timing of anti-CD137 mAb treatment relative to a viral infection has either an
immunosuppressive effect, or an immune enhancing effect. This observation is critical to the
clinical use of anti-CD137 mAbs that are currently in Phase II clinical trials to treat melanoma
and ovarian cancer and may be used as vaccine adjuvants for treating infectious diseases. In
addition to these studies our lab is focused on the following objectives: (1) Our recent studies
have led us to the hypothesis that CD137 functions in part by maintaining the survival or
function of regulatory T cells in mammals. These T cells play a critical role in the suppression of
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