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Published on: September 1, 2018
CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In Vivo
Eleonora Vannini1,2, Elisabetta Mori3, Elena Tantillo1
1Neuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy.
Abstract:
Current strategies for glioma treatment are only partly effective because of the poor selectivity for tumoral cells. Hence, the necessity to identify novel approaches is urgent. Recent studies highlighted the effectiveness of the bacterial protein cytotoxic necrotizing factor 1 (CNF1) in reducing tumoral mass, increasing survival of glioma-bearing mice and protecting peritumoral neural tissue from dysfunction. However, native CNF1 needs to be delivered into the brain, because of its incapacity to cross the blood-brain barrier (BBB) per se, thus hampering its clinical translation. To allow a non-invasive administration of CNF1, we here developed a chimeric protein (CTX-CNF1) conjugating CNF1 with chlorotoxin (CTX), a peptide already employed in clinics due to its ability of passing the BBB and selectively binding glioma cells. After systemic administration, we found that CTX-CNF1 is able to target glioma cells and significantly prolong survival of glioma-bearing mice. Our data point out the potentiality of CTX-CNF1 as a novel effective tool to treat gliomas.
Insights
A new chimeric protein, CTX-CNF1, effectively targets glioma cells and crosses the blood-brain barrier. This novel approach shows potential for treating gliomas by reducing tumor mass and increasing survival rates.
Area of Science:
- Neuro-oncology
- Biotechnology
- Protein engineering
Background:
- Current glioma treatments lack tumor selectivity, necessitating novel therapeutic strategies.
- Bacterial cytotoxic necrotizing factor 1 (CNF1) shows promise in reducing glioma mass and improving survival but cannot cross the blood-brain barrier (BBB).
Purpose of the Study:
- To develop a non-invasive method for delivering CNF1 across the BBB for glioma treatment.
- To create a chimeric protein, CTX-CNF1, by conjugating CNF1 with chlorotoxin (CTX).
Main Methods:
- Conjugation of CNF1 with chlorotoxin (CTX) to create the chimeric protein CTX-CNF1.
- Systemic administration of CTX-CNF1 in glioma-bearing mice models.
- Evaluation of CTX-CNF1's ability to target glioma cells and cross the BBB.
Main Results:
- CTX-CNF1 successfully crossed the BBB and targeted glioma cells after systemic administration.
- CTX-CNF1 significantly reduced tumoral mass and prolonged survival in glioma-bearing mice.
- Peritumoral neural tissue protection from dysfunction was observed.
Conclusions:
- CTX-CNF1 represents a promising novel therapeutic tool for glioma treatment.
- The chimeric protein enables non-invasive administration and effective targeting of gliomas.
- This approach overcomes the BBB limitation of native CNF1 for potential clinical translation.
