{"677473":{"#nid":"677473","#data":{"type":"event","title":"PhD Defense by Ali Zamat","body":[{"value":"\u003Cp\u003EAli Zamat\u003Cbr\u003EBME PhD Defense Presentation\u003Cbr\u003E\u003Cbr\u003E\u003Cstrong\u003EDate\u003C\/strong\u003E: 2024-10-22\u003Cbr\u003E\u003Cstrong\u003ETime\u003C\/strong\u003E: 2:00PM - 4:00PM\u003Cbr\u003E\u003Cstrong\u003ELocation \/ Meeting Link\u003C\/strong\u003E: Marcus Nanotechnology Building Room 1116 \/ \u003Ca href=\u0022https:\/\/gatech.zoom.us\/j\/6841027233?pwd=LzFSbU9oM045bkMzVCtXZDRwcnFBZz09\u0022\u003Ehttps:\/\/gatech.zoom.us\/j\/6841027233?pwd=LzFSbU9oM045bkMzVCtXZDRwcnFBZz09\u003C\/a\u003E\u0026nbsp;\u003Cbr\u003E\u003Cbr\u003E\u003Cstrong\u003ECommittee Members:\u003C\/strong\u003E\u003Cbr\u003EGabe A. Kwong, PhD; Costas D. Arvanitis, PhD; Susan Thomas, PhD; Sarwish Rafiq, PhD; John Blazeck, PhD\u003Cbr\u003E\u003Cbr\u003E\u003Cbr\u003E\u003Cstrong\u003ETitle\u003C\/strong\u003E: Tumor-Localized Control of CAR T cells to Potentiate Solid Tumor Immunotherapy\u003Cbr\u003E\u003Cbr\u003E\u003Cstrong\u003EAbstract:\u003C\/strong\u003E\u003Cbr\u003EChimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of several hematological malignancies, achieving durable remissions in patients with B cell cancers. However, its efficacy against solid tumors remains limited due to challenges such as antigen heterogeneity, an immunosuppressive tumor microenvironment (TME), and the scarcity of tumor-specific antigens (TSAs). These obstacles not only impede T cell infiltration, activation, and persistence within tumors but also increase the risk of off-tumor toxicity due to the expression of tumor-associated antigens (TAAs) by healthy tissues. Addressing these barriers is crucial to unlock the full potential of CAR T cell therapy for solid tumor treatment. This thesis focuses on developing tumor-localized strategies to potentiate CAR T cell-mediated immunity against solid tumors. I first develop thermal gene switches that enable remote control of gene expression in primary human and murine T cells in response to mild hyperthermia. By integrating these thermal switches with CAR T cells engineered to produce immunomodulators such as interleukin-15 superagonist (IL-15 SA) and bispecific T cell engagers (BTEs), I demonstrate that localized photothermal heating triggers the expression of therapeutic proteins within the TME to enhance intratumoral activity of CAR T cells. I then demonstrate that surface conjugation anisotropic gold nanoassemblies (GNAs) to thermal sensitive CAR T cells enables multimodal photoacoustic imaging and photothermal therapy to non-invasively monitor trafficking of CAR T cells and enhance antitumor activity against heterogeneous solid tumors. Next, to combat the immunosuppressive effects of the TME, I demonstrate that focused ultrasound-mediated hyperthermia locally triggers the expression of BTEs to redirect CAR T cell cytotoxicity towards the immunosuppressive brain tumors by depleting myeloid derived suppressor cells (MDSCs), leading to significant tumor regression in glioblastoma. Finally, I engineer synthetic antigens to sensitize solid tumors to CAR T cell therapy and bypass the need for tumor antigen discovery. I deliver VHH as an mRNA-encoded synthetic antigen using lipid nanoparticles (LNPs) which can be targeted by \u03b1VHH CAR T cells to significantly reduce tumor burden, mitigate antigen escape, and improve survival. Collectively, this thesis provides a foundation for tumor-localized control of CAR T cells to improve therapeutic responses against solid tumors.\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003ETumor-Localized Control of CAR T cells to Potentiate Solid Tumor Immunotherapy\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Tumor-Localized Control of CAR T cells to Potentiate Solid Tumor Immunotherapy"}],"uid":"27707","created_gmt":"2024-10-10 21:41:20","changed_gmt":"2024-10-10 21:41:52","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2024-10-22T14:00:00-04:00","event_time_end":"2024-10-22T16:00:00-04:00","event_time_end_last":"2024-10-22T16:00:00-04:00","gmt_time_start":"2024-10-22 18:00:00","gmt_time_end":"2024-10-22 20:00:00","gmt_time_end_last":"2024-10-22 20:00:00","rrule":null,"timezone":"America\/New_York"},"location":"Marcus Nanotechnology Building Room 1116 ","extras":[],"groups":[{"id":"221981","name":"Graduate Studies"}],"categories":[],"keywords":[{"id":"100811","name":"Phd Defense"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1788","name":"Other\/Miscellaneous"}],"invited_audience":[{"id":"78771","name":"Public"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}