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Evaluating vacquinol-1 in rats carrying glioblastoma models RG2 and NS1
Jonatan Ahlstedt1, Karolina Förnvik1, Shaian Zolfaghari1
1Rausing Laboratory, Division of Neurosurgery, Department of Clinical Sciences Lund, Lund University, Lund, Sweden, Lund University, Sweden.
Abstract:
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, and available experimental and routine therapies result in limited survival benefits. A vulnerability of GBM cells to catastrophic vacuolization and cell death, a process termed methuosis, induced by Vacquinol-1 (VQ-1) has been described earlier. In the present study, we investigate the efficacy of VQ-1 treatment in two syngeneic rat GBM models, RG2 and NS1. VQ-1 treatment affected growth of both RG2 and NS1 cells in vitro. Intracranially, significant reduction in RG2 tumor size was observed, although no effect was seen on overall survival. No survival advantage or effect on tumor size was seen in animals carrying the NS1 models compared to untreated controls. Furthermore, immunological staining of FOXP3, CD4 and CD8 showed no marked difference in immune cell infiltrate in tumor environment following treatment. Taken together, a survival advantage of VQ-1 treatment alone could not be demonstrated here, even though some effect upon tumor size was seen. Staining for immune cell markers did not indicate that VQ-1 either reduced or increased host anti-tumor immune response.
Insights
Vacquinol-1 (VQ-1) showed some effect on glioblastoma (GBM) tumor size in rats but did not improve survival. This brain tumor drug did not alter the host anti-tumor immune response in tested models.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Pharmacology
Background:
- Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with poor prognosis.
- Current therapies offer limited survival benefits for GBM patients.
- Vacquinol-1 (VQ-1) induces methuosis, a form of cell death, in GBM cells.
Purpose of the Study:
- To evaluate the efficacy of Vacquinol-1 (VQ-1) in preclinical rat models of glioblastoma.
- To assess the impact of VQ-1 on tumor growth, survival, and immune response in GBM models.
Main Methods:
- In vitro assessment of VQ-1 effects on RG2 and NS1 GBM cell lines.
- Intracranial implantation of RG2 and NS1 cells in syngeneic rats.
- Monitoring tumor size and animal survival following VQ-1 treatment.
- Immunohistochemical analysis of immune cell markers (FOXP3, CD4, CD8) in tumor tissues.
Main Results:
- VQ-1 treatment inhibited the growth of RG2 and NS1 GBM cells in vitro.
- A significant reduction in RG2 tumor size was observed after intracranial VQ-1 treatment.
- No significant improvement in overall survival was detected in either the RG2 or NS1 models.
- VQ-1 treatment did not alter the infiltration of CD4, CD8, or FOXP3 positive immune cells within the tumors.
Conclusions:
- Single-agent Vacquinol-1 (VQ-1) demonstrated limited efficacy in glioblastoma rat models, with no survival benefit observed.
- While VQ-1 affected tumor size in one model, it did not enhance the host anti-tumor immune response.
- Further investigation into combination therapies or alternative treatment strategies may be warranted for GBM.
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