Introduction: IL13Ra2 is a well-established target for novel therapies in glioblastoma (GBM) due to its overexpression on tumor cells as well as glioma-initiating cells. IL13Ra2-targeted GBM therapies have reached completion of several clinical trials, including a phase III trial. Recent studies have found that the expression of IL13Ra2, like other tumor-associated antigens, in GBM is heterogeneous and, therefore, better targeting strategies for its clinical application would be useful. This study investigated the effectiveness of different patterns of IL13Ra2 expression on the survival of syngeneic rodent glioma models. This study also aims to act as a blueprint for further tests of the level of immune response to the target immunotherapy in immunocompetent mice bearing gliomas with different levels of IL13Ra2 expression.
Methods: G26 murine glioma cell lines expressing hIL13Ra2 plasmid (G26-H2) or vector control (G26-V2) were used. Cells were FACS-sorted for IL13Ra2 expression. Ten C57Bl/6 mice were intracranially injected with G26-H2 cells (positive for hIL13Ra2) and ten received G26-V2 (negative for hIL13Ra2). The metric analyzed for outcome was survival.
Results: Two populations of G26 glioma cell lines were established per hIL13Ra2 expression: the hIL13Ra2+ and the hIL13Ra2-. In vivo, the cell lines showed a significant difference in survival: the group that received intracranial injection of G26-H2 cells (100% positive for hIL13Ra2) had a median survival of 29.5 days compared to 49 days for group receiving G26-V2 cells (100% negative for h IL13Ra2), p <0.0172.
Conclusions: We assessed two different populations of G26 glioma cell lines: h IL13Ra2+ and h IL13Ra2-. In vivo, after intracranial implantation, the two populations showed a significant difference in survival. These results confirm the role of hIL13Ra2 overexpression in specific subtypes of glioblastomas, and most likely the most aggressive ones. Immunological characterization of the tumor-bearing animals is in progress.
Patient Care: The role of hIL13Rα2 overexpression in specific subtypes of glioblastomas should be better characterized to tailor treatments for GBM patients.
Learning Objectives: Partcipants should be able to describe two variants in the G26 cell line based on hIL13Ra2 expression and should conclude that the most aggressive one is positive for hIL13Ra2