{"692535":{"#nid":"692535","#data":{"type":"event","title":"PhD Proposal by Ching Shen (Sean) Chan","body":[{"value":"\u003Cp\u003EChing Shen (Sean) Chan\u003Cbr\u003EBME PhD Proposal Presentation\u003Cbr\u003E\u003Cbr\u003EDate: 2026-09-22\u003Cbr\u003ETime: 3.00-5.00pm\u003Cbr\u003ELocation \/ Meeting Link: Marcus Nanotechnology Research Center, Room 1117-1118\u003Cbr\u003E\u003Cbr\u003ECommittee Members:\u003Cbr\u003EGabriel A. Kwong, PhD (Advisor); Philip Santangelo, PhD; Alexander Vlahos, PhD; Nicole Schmitt, MD, FACS; Rama Rao Amara, PhD\u003Cbr\u003E\u003Cbr\u003E\u003Cbr\u003ETitle: Enhancing In Vivo CAR T Cell Therapy Through mRNA Delivery to Virus-Specific T Cells\u003Cbr\u003E\u003Cbr\u003EAbstract:\u003Cbr\u003EChimeric antigen receptor (CAR) T cell therapy uses an engineered receptor that combines an extracellular antigen-recognition domain with intracellular T cell signaling domains, redirecting T cells to recognize and eliminate tumor cells independent of MHC restriction. This approach has transformed treatment for relapsed and refractory hematologic malignancies. CD19- and BCMA-directed CAR T products produce high response rates in heavily pretreated patients, with a median response rate of 66.4% across trials leading to FDA approval. Despite this efficacy, only 20% to 30% of eligible patients ultimately receive CAR T therapy. This gap stems primarily from the cost and complexity of manufacturing: each product is generated individually through leukapheresis, viral transduction, and ex vivo expansion under GMP conditions, driving per-patient costs that typically exceed $400,000 and can surpass $1 million. These constraints have shifted recent interest in the field toward in vivo engineering, in which CAR constructs are delivered directly to T cells within the patient, removing the need for ex vivo manufacturing. Current delivery strategies, however, broadly target T cells irrespective of antigen specificity or activation state. Naive T cells, a substantial fraction of the endogenous repertoire, are comparatively poor cytotoxic effectors relative to effector and memory T cells. Broad activation of the remaining repertoire can also potentially cause toxicity and break self-tolerance by activating self-reactive T cell clones. Our lab previously developed lipid nanoparticles (LNPs) surface-functionalized with peptide-major histocompatibility complex (pMHC) class I molecules, termed antigen-presenting nanoparticles (APNs), to deliver mRNA in vivo to virus-specific T cells. APNs engage the T cell receptor directly, restricting cargo delivery to T cells of a defined antigen specificity while leaving the broader T cell repertoire unperturbed. In this thesis proposal, we adapt the APN platform for in vivo CAR T cell therapy. In Aim 1, we redirect influenza-specific T cells to express a BCMA-targeted CAR in a multiple myeloma rodent model, demonstrating both APN-mediated in vivo CAR generation and the antitumor efficacy of the resulting CAR T cells. Virus-specific T cells, however, occur at low frequency within the endogenous repertoire, which limits the number of CAR-expressing effector cells generated through direct in vivo transfection alone. In Aim 2, we will use APNs to expand the target T cell population prior to in vivo CAR transfection, increasing the effector-to-target ratio to improve therapeutic outcomes. In Aim 3, we will evaluate the tolerability of APN in a non-human primate model to assess the translational potential of this approach. Successful completion of these aims will establish APNs as a platform for in vivo CAR T cell engineering, providing a lower cost alternative to ex vivo CAR T cell therapy.\u0026nbsp;\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EEnhancing In Vivo CAR T Cell Therapy Through mRNA Delivery to Virus-Specific T Cells\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Enhancing In Vivo CAR T Cell Therapy Through mRNA Delivery to Virus-Specific T Cells"}],"uid":"27707","created_gmt":"2026-09-11 13:39:09","changed_gmt":"2026-09-11 13:39:40","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2026-09-22T15:00:00-04:00","event_time_end":"2026-09-22T17:00:00-04:00","event_time_end_last":"2026-09-22T17:00:00-04:00","gmt_time_start":"2026-09-22 19:00:00","gmt_time_end":"2026-09-22 21:00:00","gmt_time_end_last":"2026-09-22 21:00:00","rrule":null,"timezone":"America\/New_York"},"location":"Marcus Nanotechnology Research Center, Room 1117-1118","extras":[],"groups":[{"id":"221981","name":"Graduate Studies"}],"categories":[],"keywords":[{"id":"102851","name":"Phd proposal"}],"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":""}}}