Andrew D. Weinberg, Ph.D.

  • Molecular Microbiology and Immunology Graduate Program, School of Medicine
  • Program in Molecular and Cellular Biosciences, School of Medicine

Biography

The main focus of the lab is to understand T cell activation during disease states. We have explored ways to manipulate the fate of antigen-specific T cells to enhance tumor-specific memory in hosts with cancer or downregulate antigen-specific responses in autoimmune disease. A challenge for immunologists has been to identify the antigen-specific cells within an inflammatory site and activate or downregulate their function in vivo. We have found a cell surface marker OX40 (CD134) that is expressed on the activated antigen-specific T cells within the site of inflammation, but not on peripheral T cells. This protein is a TNF-receptor family member that has potent costimulatory properties when crosslinked both in vitro and in vivo. We have used OX40 specific antibodies to expand tumor-reactive T cells in mice with cancer, ultimately resulting in a percentage of tumor-free mice. In contrast, we have used a deleting form of the OX40 antibody to destroy detrimental T cells in autoimmune disease, which ameliorates ongoing signs of clinical disease. By controlling the fate of antigen-specific T cells during inflammatory events, we are able to reduce or enhance T cell function in vivo, which ultimately alters the outcome of antigen-specific immunity. Currently, the lab has been trying to understand the intracellular mechanisms that lead to T cell survival once the OX40 receptor is engaged. Our goal is to enhance effector T cell survival in order to increase memory T cell development to maximize a long-term response to a particular antigen. Future projects include enhancing T cell memory to tumor antigens via OX40 agonists and performing immune-based analyses of a phase I clinical trial in cancer patients treated with anti-OX40.

Memberships and associations

  • Molecular Microbiology &Immunology Program in Molecular &Cellular Biosciences

Publications

Publications

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