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
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.
