{"304961":{"#nid":"304961","#data":{"type":"event","title":"Immunoengineering Seminar","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003E\u0022Engineering the Immune Response to \u0027Self\u0027 for Effective Cancer Immunotherapy\u0022\u003Cbr \/\u003E\u003Cbr \/\u003EMichelle Krogsgaard, PhD\u003Cbr \/\u003EAssistant Professor\u003Cbr \/\u003EPerlmutter Cancer Institute \u0026amp; Department of Pathology\u003Cbr \/\u003ENew York University School of Medicine\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cbr \/\u003E\u003C\/p\u003E\u003Cp\u003EMichelle Krogsgaard, Perlmutter Cancer Institute and Department of Pathology, NYU School of Medicine, New York, NY 10016. T-cells play a critical role in host defense against viruses, intra- and extracellular microbes, and tumors. Because foreign antigen is presented amongst a vast majority of self-antigens, T-cells have evolved the unique ability to discriminate \u201cself\u201d from \u201cnon-self\u201d with high sensitivity and selectivity, enabling the elimination of foreign pathogens while largely avoiding self-reactivity. However, tissue-specific autoimmunity and tolerance to or eradication of cancer does not fit neatly into the self\/non-self paradigm because the T-cell responses in these situations are not directed to an exogenous pathogen, but rather most often to non-mutated self-proteins. Therefore, an important question is how the immune system establishes suitable thresholds that allow positively selected T-cells to interact with self-ligands in the periphery without causing overt activation. One hypothesis to explain how a T-cell distinguishes among different types of self-ligands is the kinetic proof-reading (KP) theory, which relates signaling efficacy to the life-time of the TCR-pMHC interaction. More recently, T-cell maturation associated signaling feedback pathways have also been hypothesized to play a role in T-cell discrimination of between self-ligands. We are taking a variety of biophysical and cellular imaging approaches to determine how specific thresholds for T-cell recognition of self-antigens are set. Our recent results indicate that antitumor activity and autoimmunity are coupled and have a similar kinetic threshold; reducing autoimmunity cannot be accomplished without sacrificing efficacy of tumor killing. Therefore, an \u201coptimal TCR affinity range\u201d that leads to optimal tumor regression and minimal autoimmunity is elusive and treatment strategies focusing on increasing TCR affinities to a supraphysiological level has most likely little therapeutic benefit. New strategies to overcome this issue includes engineering of TCRs and T-cell signaling pathways to carefully balance tumor-reactivity and autoimmunity. Supported by NIH, The American Cancer Society, The Pew Trust and The Cancer Research Institute.\u003C\/p\u003E\u003Cp\u003E\u003Cbr \/\u003E\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EImmunoengineering Seminar - \u0022Engineering the Immune Response to \u0027Self\u0027 for Effective Cancer Immunotherapy\u0022 -\u0026nbsp;Michelle Krogsgaard, PhD - New York University School of Medicine\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"\u0022Engineering the Immune Response to \u0027Self\u0027 for Effective Cancer Immunotherapy\u0022 - Michelle Krogsgaard, PhD - New York University School of Medicine"}],"uid":"27195","created_gmt":"2014-06-25 08:40:21","changed_gmt":"2017-04-13 21:22:24","author":"Colly Mitchell","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2014-10-02T12:00:00-04:00","event_time_end":"2014-10-02T13:00:00-04:00","event_time_end_last":"2014-10-02T13:00:00-04:00","gmt_time_start":"2014-10-02 16:00:00","gmt_time_end":"2014-10-02 17:00:00","gmt_time_end_last":"2014-10-02 17:00:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"related_links":[{"url":"http:\/\/www.med.nyu.edu\/biosketch\/krogsm01\/","title":"Krogsgaard profile"},{"url":"http:\/\/immunoengineering.gatech.edu\/","title":"Immunoengineering website"}],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"}],"categories":[],"keywords":[{"id":"248","name":"IBB"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1795","name":"Seminar\/Lecture\/Colloquium"}],"invited_audience":[{"id":"78751","name":"Undergraduate students"},{"id":"78761","name":"Faculty\/Staff"},{"id":"174045","name":"Graduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022mailto:krishnendu.roy@bme.gatech.edu\u0022\u003EKrishnendu Roy, PhD\u003C\/a\u003E\u003C\/p\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}