LECTURE SERIES - INTERLEUKIN 13 (IL13) 

IL13appt.PNG
IL13bppt.PNG

Interleukin-13 | IL13

Hyperbaric Oxygen Therapy elevates IL13

 - IL-13 is a cytokine found to promote IgE class switching and powerfully inhibits proinflammatory cytokines.

 - In patients with Multiple Sclerosis high IL-13 levels in the CSF are reported to be neuroprotective, anti-excitotoxic effect.

 - IL-13 enhances neuronal integrity and synaptic function in patients with MS.  

 - IL-13 specifically induces physiological changes in parasitized organs that are required to expel the offending organisms or their products. For example, expulsion from the gut of a variety of mouse helminths requires IL-13 secreted by Th2 cells.  IL-13 induces several changes in the gut that create an environment hostile to the parasite, including enhanced contractions and glycoprotein hyper-secretion from gut epithelial cells, that ultimately lead to detachment of the organism from the gut wall and their removal.  

Hyperbaric Oxygenation of Hypoxic Glioblastoma Multiforme Cells Potentiates the Killing Effect of an Interleukin-13-Based Cytotoxin

 - IL13 has anti-tumour effects and when combined with HBO enhances the killing effects of Glioblastoma and other cancers. 

 - Interleukin-13 receptor-targeted cytotoxin (IL13-PE38) is highly cytotoxic to human glioblastoma (GBM) cells.

Mol Ther. 2018 Jan 3;26(1):31-44. doi: 10.1016/j.ymthe.2017.10.002. Epub 2017 Oct 5.

Optimization of IL13Rα2-Targeted Chimeric Antigen Receptor T Cells for Improved Anti-tumor Efficacy against Glioblastoma.

T cell immunotherapy is emerging as a powerful strategy to treat cancer and may improve outcomes for patients with glioblastoma (GBM). We have developed a chimeric antigen receptor (CAR) T cell immunotherapy targeting IL-13 receptor α2 (IL13Rα2) for the treatment of GBM. Here, we describe the optimization of IL13Rα2-targeted CAR T cells, including the design of a 4-1BB (CD137) co-stimulatory CAR (IL13BBζ) and a manufacturing platform using enriched central memory T cells. Utilizing orthotopic human GBM models with patient-derived tumor sphere lines in NSG mice, we found that IL13BBζ-CAR T cells improved anti-tumor activity and T cell persistence as compared to first-generation IL13ζ-CAR CD8+ T cells that had shown evidence for bioactivity in patients. Investigating the impact of corticosteroids, given their frequent use in the clinical management of GBM, we demonstrate that low-dose dexamethasone does not diminish CAR T cell anti-tumor activity in vivo. Furthermore, we found that local intracranial delivery of CAR T cells elicits superior anti-tumor efficacy as compared to intravenous administration, with intraventricular infusions exhibiting possible benefit over intracranial tumor infusions in a multifocal disease model. Overall, these findings help define parameters for the clinical translation of CAR T cell therapy for the treatment of brain tumors.

 

OXYMED Australia

643 Chapel Street South Yarra 3141 Australia

T: +61 3 9826 9898  E: info@oxymed.com.au  

All former rights reserved 2020