{ "96254-21792188": { "datetime_modified":"20220726T130939", "datetime_start":"20220729T100000", "datetime_end":"20220729T110000", "has_end_time":1, "date_start":"2022-07-29", "date_end":"2022-07-29", "time_start":"10:00:00", "time_end":"11:00:00", "time_zone":"America\/Detroit", "event_title":"Discovery and Development of Agonist Antibodies for T Cell Receptors", "occurrence_title":"", "combined_title":"Discovery and Development of Agonist Antibodies for T Cell Receptors: BME PhD Defense: Harkamal Jhajj", "event_subtitle":"BME PhD Defense: Harkamal Jhajj", "event_type":"Lecture \/ Discussion", "event_type_id":"13", "description":"Agonist antibodies that activate co-stimulatory immune receptors, such as the tumor necrosis factor (TNF) receptors OX40 and CD137, are an important class of emerging therapeutics due to their ability to regulate immune cell activity. Despite their promise, there are no approved agonist antibodies for treating cancer as demonstrated by previous unsuccessful clinical trials. Although multiple factors are responsible for poor clinical efficacy, one major bottleneck is the reliance on Fc\u03b3R-mediated crosslinking for sufficient receptor activation. This is inherently problematic because Fc\u03b3R expression varies greatly on different immune cells, leading to a wide range of receptor agonism. Emerging research suggests that antibodies engaging two different epitopes on the same immune receptor mediate receptor superclustering and enable robust antibody agonism without extrinsic Fc crosslinking. However, there are no systematic methods for identifying such biepitopic (also known as biparatopic) agonist antibodies. Therefore, the objective of this research work is to develop facile methods for reliably identifying biepitopic antibodies to activate immune receptors for immunotherapeutic applications.\r\n\r\nBiepitopic antibodies have been shown to mediate potent receptor activation for a variety of immune receptors. Traditionally, the generation of these antibodies requires key steps including animal immunization, epitope binning to identify unique antibody pairs, and combining antibody pairs to engineer biepitopic antibodies. While this approach has been used to successfully discover biepitopic antibodies, it suffers from key limitations. Notably, animal immunization and subsequent antibody isolation is an arduous and unpredictable process. Even when successful clones are discovered from these processes, further epitope binning experiments are needed to select antibody pairs to discover potent immune therapeutics. To overcome these limitations, we developed an antibody screening strategy that greatly simplifies the discovery of biepitopic antibodies. Our approach eliminates the need for animal immunization by using existing, off-the-shelf IgG antibodies specific to the target receptor. Next, we perform in vitro selections by blocking the receptor epitope of the existing antibody and conducting subsequent sorts to identify single-chain antibodies with orthogonal binding domains. Thus far, our work has shown that the antibody screening strategy can be used to discover antibodies for a variety of TNF receptors including OX40 and CD137.\r\n\r\nGiven that receptor clustering of three or more receptors is critical for activating TNF receptors, we first generated biepitopic tetravalent OX40 antibodies by attaching novel single-chain antibodies to the C-termini of the light chain of existing clinical-stage antibodies. These tetravalent biepitopic antibodies showed remarkable T cell proliferation and cytokine secretion for biepitopic antibodies compared to their monoepitopic counterparts. Next, we sought to improve the additional clinical-stage OX40 IgGs engineered as biepitopic antibodies to show the generality of our findings that biepitopic antibodies can mediate superior and Fc\u03b3R-independent activities. Beyond OX40 IgGs, we also show that biepitopic antibodies can be used to mediate superior T cell proliferation for other TNF receptors including CD137. Looking forward, we anticipate that these research advancements will accelerate the discovery and development of the next generation of immune therapeutics.\r\n\r\nDate: Friday, July 29, 2022\r\nTime: 10:00 AM\r\nZoom: https:\/\/umich.zoom.us\/j\/5163583658\r\nCo-Chairs: Professors Peter Tessier and Lonnie Shea", "occurrence_notes":null, "guid":"96254-21792188@events.umich.edu", "permalink":"http:\/\/events.umich.edu\/event\/96254", "building_id":"null", "building_name":"Off Campus Location", "campus_maps_id":"1", "room":"", "location_name":"Virtual", "has_livestream":1, "livestream_type":"zoom", "livetream_require_login":0, "livestream_id":"5163583658", "livestream_link":"https:\/\/umich.zoom.us\/j\/5163583658", "cost":"", "tags":["Basic Science","biomedical","biomedical engineering","Biosciences","bme","engineering","Life Science","Medicine","Michigan Engineering","Science"], "website":"", "sponsors":[ { "group_name":"Biomedical Engineering", "group_id":"1143", "website":"https:\/\/www.facebook.com\/profile.php?id=100094127215673" } ], "image_url":"https:\/\/events.umich.edu\/media\/attachments\/2022\/07\/event_96254_original-1.png", "styled_images":{ "event_thumb":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_thumb\/media\/attachments\/2022\/07\/event_96254_original-1.png", "event_large":"https:\/\/events.umich.edu\/media\/cache\/event_large\/media\/attachments\/2022\/07\/event_96254_original-1.png", "event_large_2x":"https:\/\/events.umich.edu\/media\/cache\/event_large_2x\/media\/attachments\/2022\/07\/event_96254_original-1.png", "event_large_lightbox":"https:\/\/events.umich.edu\/media\/cache\/event_large_lightbox\/media\/attachments\/2022\/07\/event_96254_original-1.png", "group_thumb":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_thumb\/media\/attachments\/2022\/07\/event_96254_original-1.png", "group_thumb_square":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_thumb_square\/media\/attachments\/2022\/07\/event_96254_original-1.png", "group_large":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_large\/media\/attachments\/2022\/07\/event_96254_original-1.png", "group_large_lightbox":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_large_lightbox\/media\/attachments\/2022\/07\/event_96254_original-1.png", "event_large_crop":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_large_crop\/media\/attachments\/2022\/07\/event_96254_original-1.png", "event_list":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_list\/media\/attachments\/2022\/07\/event_96254_original-1.png", "event_list_2x":"https:\/\/events.umich.edu\/media\/cache\/event_list_2x\/media\/attachments\/2022\/07\/event_96254_original-1.png", "event_grid":"https:\/\/events.umich.edu\/media\/cache\/event_grid\/media\/attachments\/2022\/07\/event_96254_original-1.png", "event_grid_2x":"https:\/\/events.umich.edu\/media\/cache\/event_grid_2x\/media\/attachments\/2022\/07\/event_96254_original-1.png", "event_feature_large":"https:\/\/events.umich.edu\/media\/cache\/event_feature_large\/media\/attachments\/2022\/07\/event_96254_original-1.png", "event_feature_thumb":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_feature_thumb\/media\/attachments\/2022\/07\/event_96254_original-1.png" }, "occurrence_count":1, "first_occurrence":21792188 } , "95912-21791428": { "datetime_modified":"20220813T063106", "datetime_start":"20220729T110000", "datetime_end":"20220729T120000", "has_end_time":1, "date_start":"2022-07-29", "date_end":"2022-07-29", "time_start":"11:00:00", "time_end":"12:00:00", "time_zone":"America\/Detroit", "event_title":"ScribeAmerica Virtual Information Session July 29th", "occurrence_title":"", "combined_title":"ScribeAmerica Virtual Information Session July 29th", "event_subtitle":"", "event_type":"Careers \/ Jobs", "event_type_id":"2", "description":"Are you looking at a future career in healthcare and need clinical experience? 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One-week courses give an overview of a methodology topic, including readings and homework. One-day workshops are offered for those who need to learn a specific technique or method in a short period of time.\r\n\r\nAll 2022 courses will be offered in an alternative remote format.", "occurrence_notes":null, "guid":"95200-21788808@events.umich.edu", "permalink":"http:\/\/events.umich.edu\/event\/95200", "building_id":"null", "building_name":"Off Campus Location", "campus_maps_id":"1", "room":"", "location_name":"Virtual", "has_livestream":0, "cost":"Fees are based upon the total number of course hours. Applicants who make their payment at the time of registration will receive a 10% discount. 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No prior experience with meditation is required. \r\n\r\n*What will you learn?*\r\n\r\nThe guided meditation practice involves three simple steps: relaxation, rejuvenation, and meditation.\r\n\r\nRelaxation brings your body to a calm, steady posture creating a stillness at the physical level, and prepares the mind for meditation. We follow this with a rejuvenation method to detox the mind to let go of stress and complex emotions, and will leave you feeling light and refreshed. Lastly, learning to meditate by being mindful of your heart will connect you with yourself by listening to your heart\u2019s voice. \r\n\r\n*Why Meditate?*\r\n\r\nWhile physical fitness keeps our bodies in shape, meditation is an exercise for the mind and mental wellness. In addition to the measurable benefits mentally and physically, many people benefit from an unquantifiable inner poise and harmony. \r\n\r\n*Please take Learn to Meditate session if you are new to the practice. 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