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Enhancing T cell therapy through TCR signaling-responsive nanoparticle drug delivery




TOPIC: Enhancing T cell therapy through TCR signaling-responsive nanoparticle drug delivery 
SPEAKER: Prof. Li Tang, École polytechnique fédérale de Lausanne (EPFL), Switzerland

TIME:July 5 (Tuesday) AM10:00  
LOCATION: Room 528, Chemistry Building A  
INVITER: Prof. Xinyuan Zhu

Abstract: Engineered synthetic biomaterials and nanomedicines hold great promise to address the most critical biomedical challenges in human healthcare. The research in Tang laboratory focuses on establishing detailed understanding of the interactions between synthetic biomaterials and the immune system and achieving precise control of the immunity using smart biomaterials in order to develop effective novel immunotherapies for cancers, infectious diseases and autoimmune disorders. In this seminar, I will discuss the most recent advances in adoptive cell therapy (ACT) for the treatment of cancer. ACT employing antigen-specific T-cells has elicited dramatic clinical responses in leukaemia and a subset of melanoma patients. However, strategies to safely and effectively augment T-cell function, especially in solid tumours, remain of great interest. Here we describe a strategy to “backpack” large quantities of supporting protein drugs on T-cells, using protein nanogels (NGs) that selectively release adjuvant drugs in response to TCR triggering, focusing drug release in sites of antigen encounter such as the tumour microenvironment. We show that T-cells increase their cell surface reduction potential on activation, which we exploit through the design of cell surface-conjugated NGs that disassemble to release protein cargos in response to this change in the local reductive environment following TCR triggering. Using an IL-15 superagonist as a candidate adjuvant drug cargo, we demonstrate that relative to systemic administration of free cytokines, NG delivery selectively expands T-cells 15-fold in tumours, and allows at least 8-fold higher doses of cytokine to be administered without toxicity, leading to substantially increased anti-tumour efficacy. This strategy provides a general approach to augment the function of cell therapies by linking drug release to cell function in vivo.
At the end of the talk, I will also discuss how to apply for the prestigious PhD programs at EPFL (ranked top 20 universities all over the world in the 2015-2016 QS ranking). We welcome talented and motivated students to apply for doctoral and postdoctoral research positions in Tang lab at EPFL.


Biography: Li Tang received his B.S. in Chemistry from Peking University in China in 2007, and his Ph.D. in Materials Science and Engineering from University of Illinois at Urbana-Champaign, USA, in 2012, under the supervision of Prof. Jianjun Cheng. He was an Irvington Postdoctoral Fellow in the laboratory of Prof. Darrell Irvine at Massachusetts Institute of Technology during 2013-2016. He joined the faculty of Institute of Bioengineering, and Institute of Materials Science & Engineering, at École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland, as Tenure-Track Assistant Professor in 2016. His research focuses on modulating the immune system using smart biomaterials to develop novel vaccines and immunotherapies. Dr. Tang is the recipient of Irvington Postdoctoral Fellowship from Cancer Research Institute, Young Investigator Travel Award from Society for Immunotherapy of Cancer, Marlena Felter Bradford Research Travel Fellowship, M-CNTC Fellowship from National Cancer Institute Alliance for Nanotechnology in Cancer, and Racheff-Intel Award from University of Illinois.