The use of interleukin 12-secreting neural stem cells for the treatment of intracranial glioma.
Neural stem cells (NSCs) are capable of tracking migrating glioma cells. To exploit this tropism to generate an antitumor T-cell response, particularly against disseminating tumor pockets, we inoculated intracranial glioma-bearing mice with interleukin 12 (IL-12) producing NSCs. Intratumoral therapy with IL-12-secreting NSCs prolonged survival compared to treatment with nonsecretory NSCs or saline. NSCs demonstrated strong tropism for disseminating glioma, and IL-12-secreting NSC therapy was associated with enhanced T-cell infiltration in tumor microsatellites and long-term antitumor immunity. These results indicate that the use of tumor tracking NSCs represents a potent new therapeutic modality for glioma.
Ehtesham
Moneeb
M
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Kabos
Peter
P
Kabosova
Andrea
A
Neuman
Toomas
T
Black
Keith L
KL
Yu
John S
JS
D016475:3T3 Cells; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D009836:Oligodendroglia / Q000166:cytology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000096:biosynthesis
D018664:Interleukin-12; D001616:beta-Galactosidase