• CTX-CNF1
• Glioblastoma
• Glioblastoma Multiforme
• Immune Checkpoint Inhibitors (ICI)

Glioblastoma Multiforme (GBM) is the most aggressive and malignant form of brain tumours. The therapeutic strategies currently used to counteract GBM are not effective, and the consequent average survival is of about 15 months after diagnosis (Leece et al., 2017; Ostrom et al., 2021). Hence, there is an urgent need to identify innovative and effective therapeutic approaches that might produce a real impact on GBM patients’ survival and quality of life.
In Dr. Vannini’s lab has been recently designed and tested a chimeric protein, CTX-CNF1, as a potential drug to counteract GBM (Vannini et al., 2021). In vitro studies have highlighted that CTX-CNF1 induces senescence and death in both murine and human GBM cells, whereas in vivo studies had shown that CTX-CNF1 selectively targets glioma cells and increases glioma-bearing mice survival (Vannini et al., 2021). These experiments were performed on the classic and widely used GL261 mouse model. However, experiments on different GBM models are required in order to understand whether the proposed therapeutic approach might represent an effective and solid strategy.
Thus, during my Master Thesis’s internship at the Neuroscience Institute of CNR I studied the effect of CTX-CNF1 treatment on another syngeneic mouse model of GBM, i.e.: CT-2A (Riva et al., 2019). CT-2A cells were injected into the primary motor cortex. In comparison with the GL261, the CT-2A model is more infiltrative because CT-2A cells express stemness makers such as Nestin (Binello et al., 2012). Hence, this model represents a valuable tool for pre-clinical testing of novel therapeutics. In both vehicle and CTX-CNF1 treated glioma-bearing animals, I longitudinally monitored motor performances, using Grip Strength and Grid Walk tests and tumoral mass growth, through MRI. I found that CTX-CNF1 is able to prolong glioma-bearing animals survival, reducing GBM mass and maintains motor functionalities. My data also showed that CD8 cells might be the mediator CTX-CNF1 action.
Testing potential drugs on different animal models is crucial before moving to clinics, in order to better predict a treatment outcome in patients and to identify and characterize the safety associated with the administration of the proposed drug (Bugelski & Martin, 2012).