Evaluation of the Immunomodulatory Effects of Radiation for Chimeric Antigen Receptor T Cell Therapy in Glioblastoma Multiforme.

Autor: Akhavan D; Department of Radiation Oncology, University of Kansas Cancer Center, Kansas City, KS 66160, USA.; Department of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Cancer Center, Kansas City, KS 66160, USA.; Department of Cancer Biology, University of Kansas Cancer Center, Kansas City, KS 66160, USA.; Bioengineering Program, University of Kansas, Lawrence, KS 66045, USA.; Department of Immuno-Oncology, City of Hope Beckman Research Institute, Duarte, CA 91010, USA.; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.; Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA., Subham S; Department of Radiation Oncology, University of Kansas Cancer Center, Kansas City, KS 66160, USA.; Department of Cancer Biology, University of Kansas Cancer Center, Kansas City, KS 66160, USA.; Bioengineering Program, University of Kansas, Lawrence, KS 66045, USA., Jeppson JD; Department of Radiation Oncology, University of Kansas Cancer Center, Kansas City, KS 66160, USA., Aguilar B; Department of Immuno-Oncology, City of Hope Beckman Research Institute, Duarte, CA 91010, USA.; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA., Wong RA; Department of Immuno-Oncology, City of Hope Beckman Research Institute, Duarte, CA 91010, USA.; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA., Hibbard JC; Department of Immuno-Oncology, City of Hope Beckman Research Institute, Duarte, CA 91010, USA.; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA., Hui S; Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA., Wong JYC; Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA., Forman SJ; Department of Immuno-Oncology, City of Hope Beckman Research Institute, Duarte, CA 91010, USA.; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA., Alizadeh D; Department of Immuno-Oncology, City of Hope Beckman Research Institute, Duarte, CA 91010, USA.; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA., Brown CE; Department of Immuno-Oncology, City of Hope Beckman Research Institute, Duarte, CA 91010, USA.; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
Jazyk: angličtina
Zdroj: Cells [Cells] 2024 Jun 21; Vol. 13 (13). Date of Electronic Publication: 2024 Jun 21.
DOI: 10.3390/cells13131075
Abstrakt: Standard-of-care treatment for Glioblastoma Multiforme (GBM) is comprised of surgery and adjuvant chemoradiation. Chimeric Antigen Receptor (CAR) T cell therapy has demonstrated disease-modifying activity in GBM and holds great promise. Radiation, a standard-of-care treatment for GBM, has well-known immunomodulatory properties and may overcome the immunosuppressive tumor microenvironment (TME); however, radiation dose optimization and integration with CAR T cell therapy is not well defined. Murine immunocompetent models of GBM were treated with titrated doses of stereotactic radiosurgery (SRS) of 5, 10, and 20 Gray (Gy), and the TME was analyzed using Nanostring. A conditioning dose of 10 Gy was determined based on tumor growth kinetics and gene expression changes in the TME. We demonstrate that a conditioning dose of 10 Gy activates innate and adaptive immune cells in the TME. Mice treated with 10 Gy in combination with mCAR T cells demonstrated enhanced antitumor activity and superior memory responses to rechallenge with IL13Rα2-positive tumors. Furthermore, 10 Gy plus mCAR T cells also protected against IL13Rα2-negative tumors through a mechanism that was, in part, c-GAS-STING pathway-dependent. Together, these findings support combination conditioning with low-dose 10 Gy radiation in combination with mCAR T cells as a therapeutic strategy for GBM.
Databáze: MEDLINE
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