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Modulation of the gut microbiota engages antigen cross-presentation to enhance antitumor effects of CAR T cell immunotherapy.
Uribe-Herranz, Mireia; Beghi, Silvia; Ruella, Marco; Parvathaneni, Kalpana; Salaris, Silvano; Kostopoulos, Nektarios; George, Subin S; Pierini, Stefano; Krimitza, Elisavet; Costabile, Francesca; Ghilardi, Guido; Amelsberg, Kimberly V; Lee, Yong Gu; Pajarillo, Raymone; Markmann, Caroline; McGettigan-Croce, Bevin; Agarwal, Divyansh; Frey, Noelle; Lacey, Simon F; Scholler, John; Gabunia, Khatuna; Wu, Gary; Chong, Elise; Porter, David L; June, Carl H; Schuster, Stephen J; Bhoj, Vijay; Facciabene, Andrea.
Affiliation
  • Uribe-Herranz M; Division of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Immunology Department, Hospital Clínic of Barcelona, Barcelona 08036, Spain.
  • Beghi S; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Ruella M; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Lymphoma Program, Abramson Cancer Center, University o
  • Parvathaneni K; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Salaris S; Unit of Biostatistics, Epidemiology and Public Health, University of Padova, Padova, Italy.
  • Kostopoulos N; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • George SS; Bioinformatics Core, Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Pierini S; Division of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA; The Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Krimitza E; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Costabile F; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Ghilardi G; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Lymphoma Program, Abramson Cancer Center, University o
  • Amelsberg KV; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Lymphoma Program, Abramson Cancer Center, University o
  • Lee YG; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Lymphoma Program, Abramson Cancer Center, University o
  • Pajarillo R; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Lymphoma Program, Abramson Cancer Center, University o
  • Markmann C; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • McGettigan-Croce B; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Agarwal D; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Frey N; Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Lacey SF; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Scholler J; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Gabunia K; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Wu G; Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Chong E; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Porter DL; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Lymphoma Program, Abramson Cancer Center, University o
  • June CH; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Schuster SJ; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Lymphoma Program, Abramson Cancer Center, University o
  • Bhoj V; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Facciabene A; Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA; The Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA 1
Mol Ther ; 31(3): 686-700, 2023 03 01.
Article in En | MEDLINE | ID: mdl-36641624
ABSTRACT
Several studies have shown the influence of commensal microbes on T cell function, specifically in the setting of checkpoint immunotherapy for cancer. In this study, we investigated how vancomycin-induced gut microbiota dysbiosis affects chimeric antigen receptor (CAR) T immunotherapy using multiple preclinical models as well as clinical correlates. In two murine tumor models, hematopoietic CD19+-A20 lymphoma and CD19+-B16 melanoma, mice receiving vancomycin in combination with CD19-directed CAR T cell (CART-19) therapy displayed increased tumor control and tumor-associated antigens (TAAs) cross-presentation compared with CART-19 alone. Fecal microbiota transplant from human healthy donors to pre-conditioned mice recapitulated the results obtained in naive gut microbiota mice. Last, B cell acute lymphoblastic leukemia patients treated with CART-19 and exposed to oral vancomycin showed higher CART-19 peak expansion compared with unexposed patients. These results substantiate the role of the gut microbiota on CAR T cell therapy and suggest that modulation of the gut microbiota using vancomycin may improve outcomes after CAR T cell therapy across tumor types.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gastrointestinal Microbiome / Receptors, Chimeric Antigen Limits: Animals / Humans Language: En Journal: Mol Ther Journal subject: BIOLOGIA MOLECULAR / TERAPEUTICA Year: 2023 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gastrointestinal Microbiome / Receptors, Chimeric Antigen Limits: Animals / Humans Language: En Journal: Mol Ther Journal subject: BIOLOGIA MOLECULAR / TERAPEUTICA Year: 2023 Document type: Article Affiliation country: