Genetically modified IL2 bone-marrow-derived myeloid cells reprogram the glioma immunosuppressive tumor microenvironment

Alessandro Canella; Matthew Nazzaro; Sakthi Rajendran; Claire Schmitt; Abigail Haffey; Giovanni Nigita; Diana Thomas; Justin M. Lyberger; Gregory K. Behbehani; Nduka M. Amankulor; Elaine R. Mardis; Timothy P. Cripe; Prajwal Rajappa

Cell Reports (Aug 2023)

Genetically modified IL2 bone-marrow-derived myeloid cells reprogram the glioma immunosuppressive tumor microenvironment

Alessandro Canella,
Matthew Nazzaro,
Sakthi Rajendran,
Claire Schmitt,
Abigail Haffey,
Giovanni Nigita,
Diana Thomas,
Justin M. Lyberger,
Gregory K. Behbehani,
Nduka M. Amankulor,
Elaine R. Mardis,
Timothy P. Cripe,
Prajwal Rajappa

Affiliations

Alessandro Canella: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
Matthew Nazzaro: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
Sakthi Rajendran: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
Claire Schmitt: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
Abigail Haffey: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
Giovanni Nigita: Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
Diana Thomas: Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
Justin M. Lyberger: Department of Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
Gregory K. Behbehani: Department of Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, OH, USA
Nduka M. Amankulor: Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA
Elaine R. Mardis: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
Timothy P. Cripe: Center for Childhood Cancer, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH, USA
Prajwal Rajappa: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 8
p. 112891

Abstract

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Summary: Gliomas are one of the leading causes of cancer-related death in the adolescent and young adult (AYA) population. Two-thirds of AYA glioma patients are affected by low-grade gliomas (LGGs), but there are no specific treatments. Malignant progression is supported by the immunosuppressive stromal component of the tumor microenvironment (TME) exacerbated by M2 macrophages and a paucity of cytotoxic T cells. A single intravenous dose of engineered bone-marrow-derived myeloid cells that release interleukin-2 (GEMys-IL2) was used to treat mice with LGGs. Our results demonstrate that GEMys-IL2 crossed the blood-brain barrier, infiltrated the TME, and reprogrammed the immune cell composition and transcriptome. Moreover, GEMys-IL2 extended survival in an LGG immunocompetent mouse model. Here, we report the efficacy of an in vivo approach that demonstrates the potential for a cell-mediated innate immunotherapy designed to enhance the recruitment of activated effector T and natural killer cells within the glioma TME.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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