Chimeric antigen receptor (CAR) T cell therapy for glioblastoma remains challenging due to insufficient CAR T cell abundance and antigen-negative tumor cells evading targeting. Unfortunately, most preclinical studies evaluating CAR T cells in glioblastoma use tumors expressing a single antigen, xenografts, and/or lymphodepletion. While lymphodepletion enhances CAR T cell efficacy, it diminishes the endogenous immune system, which has the potential for tumor eradication. Here, we orthotopically delivered IL7 and/or Flt3L expressing CAR T cells in 50% EGFRvIII-positive and -negative tumors pre-conditioned with non-lymphodepleting irradiation. IL7 and IL7 Flt3L CAR T cells increased intratumoral CD8 CAR T cell populations seven days after treatment. IL7 co-expression with Flt3L increased conventional dendritic cells (cDCs) as well as the CD103+XCR1+ population known for migration and antigen cross-presentation. Treatment with IL7 or IL7 Flt3L CAR T cells improved overall survival to 67% and 50%, respectively, compared to 9% in vCAR and vFL and no survivors in PBS treated. However, there was no significant difference in survival between IL7 and IL7 Flt3L CAR T cells. We conclude that CAR T cells modified to express IL7 demonstrate therapeutic potential in glioblastoma treated with non-lymphodepleting irradiation and co-expression with Flt3L modestly improved intratumoral dendritic cell populations.
","abstract_html":"<p>Chimeric antigen receptor (CAR) T cell therapy for glioblastoma remains challenging due to insufficient CAR T cell abundance and antigen-negative tumor cells evading targeting. Unfortunately, most preclinical studies evaluating CAR T cells in glioblastoma use tumors expressing a single antigen, xenografts, and/or lymphodepletion. While lymphodepletion enhances CAR T cell efficacy, it diminishes the endogenous immune system, which has the potential for tumor eradication. Here, we orthotopically delivered IL7 and/or Flt3L expressing CAR T cells in 50% EGFRvIII-positive and -negative tumors pre-conditioned with non-lymphodepleting irradiation. IL7 and IL7 Flt3L CAR T cells increased intratumoral CD8 CAR T cell populations seven days after treatment. IL7 co-expression with Flt3L increased conventional dendritic cells (cDCs) as well as the CD103+XCR1+ population known for migration and antigen cross-presentation. Treatment with IL7 or IL7 Flt3L CAR T cells improved overall survival to 67% and 50%, respectively, compared to 9% in vCAR and vFL and no survivors in PBS treated. However, there was no significant difference in survival between IL7 and IL7 Flt3L CAR T cells. We conclude that CAR T cells modified to express IL7 demonstrate therapeutic potential in glioblastoma treated with non-lymphodepleting irradiation and co-expression with Flt3L modestly improved intratumoral dendritic cell populations.</p>","abstract_has_math":false,"creators":["Swan, Sheridan Leigh-Carroll"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Bellamkonda, Ravi"],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023","date_published":"2023","updated_at":"2026-07-24T02:06:59Z","subjects":["Immunology","Biomedical engineering","CAR T cells","dendritic cells","Flt3L","glioblastoma","IL7","T cell abundance"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10161/27581","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Bellamkonda, Ravi"]},{"key":"dc:creator","label":"Author","values":["Swan, Sheridan Leigh-Carroll"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2023-06-08T18:19:53Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2023-06-08T18:19:53Z"]},{"key":"dc:date.issued","label":"Date","values":["2023"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Immunology","Biomedical engineering","CAR T cells","dendritic cells","Flt3L","glioblastoma","IL7","T cell abundance"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10161/27581"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Chimeric antigen receptor (CAR) T cell therapy for glioblastoma remains challenging due to insufficient CAR T cell abundance and antigen-negative tumor cells evading targeting. Unfortunately, most preclinical studies evaluating CAR T cells in glioblastoma use tumors expressing a single antigen, xenografts, and/or lymphodepletion. While lymphodepletion enhances CAR T cell efficacy, it diminishes the endogenous immune system, which has the potential for tumor eradication. Here, we orthotopically delivered IL7 and/or Flt3L expressing CAR T cells in 50% EGFRvIII-positive and -negative tumors pre-conditioned with non-lymphodepleting irradiation. IL7 and IL7 Flt3L CAR T cells increased intratumoral CD8 CAR T cell populations seven days after treatment. IL7 co-expression with Flt3L increased conventional dendritic cells (cDCs) as well as the CD103+XCR1+ population known for migration and antigen cross-presentation. Treatment with IL7 or IL7 Flt3L CAR T cells improved overall survival to 67% and 50%, respectively, compared to 9% in vCAR and vFL and no survivors in PBS treated. However, there was no significant difference in survival between IL7 and IL7 Flt3L CAR T cells. We conclude that CAR T cells modified to express IL7 demonstrate therapeutic potential in glioblastoma treated with non-lymphodepleting irradiation and co-expression with Flt3L modestly improved intratumoral dendritic cell populations.
"]},{"key":"dc:title","label":"Title","values":["Enhancing Chimeric Antigen Receptor T cell therapy in Mouse EGFRvIII Heterogeneous Glioblastoma"]}]}],"canonical_facts":{"dc:contributor.advisor":["Bellamkonda, Ravi"],"dc:creator":["Swan, Sheridan Leigh-Carroll"],"dc:date.accessioned":["2023-06-08T18:19:53Z"],"dc:date.available":["2023-06-08T18:19:53Z"],"dc:date.issued":["2023"],"dc:description.abstract":["Chimeric antigen receptor (CAR) T cell therapy for glioblastoma remains challenging due to insufficient CAR T cell abundance and antigen-negative tumor cells evading targeting. Unfortunately, most preclinical studies evaluating CAR T cells in glioblastoma use tumors expressing a single antigen, xenografts, and/or lymphodepletion. While lymphodepletion enhances CAR T cell efficacy, it diminishes the endogenous immune system, which has the potential for tumor eradication. Here, we orthotopically delivered IL7 and/or Flt3L expressing CAR T cells in 50% EGFRvIII-positive and -negative tumors pre-conditioned with non-lymphodepleting irradiation. IL7 and IL7 Flt3L CAR T cells increased intratumoral CD8 CAR T cell populations seven days after treatment. IL7 co-expression with Flt3L increased conventional dendritic cells (cDCs) as well as the CD103+XCR1+ population known for migration and antigen cross-presentation. Treatment with IL7 or IL7 Flt3L CAR T cells improved overall survival to 67% and 50%, respectively, compared to 9% in vCAR and vFL and no survivors in PBS treated. However, there was no significant difference in survival between IL7 and IL7 Flt3L CAR T cells. We conclude that CAR T cells modified to express IL7 demonstrate therapeutic potential in glioblastoma treated with non-lymphodepleting irradiation and co-expression with Flt3L modestly improved intratumoral dendritic cell populations.
"],"dc:identifier.uri":["https://hdl.handle.net/10161/27581"],"dc:subject":["Immunology","Biomedical engineering","CAR T cells","dendritic cells","Flt3L","glioblastoma","IL7","T cell abundance"],"dc:title":["Enhancing Chimeric Antigen Receptor T cell therapy in Mouse EGFRvIII Heterogeneous Glioblastoma"],"dc:type":["Dissertation"]},"updated_at":"2026-07-24T02:06:59Z"}