Dual Targeting NG2 and GD3A Using Mab-Zap Immunotoxin Results in Reduced Glioma Cell Viability In Vitro

Background: Effective treatments for glioblastoma multiforme (GBM) are lacking due, in part, to cellular heterogeneity. Consequently, single-target therapeutic strategies are unlikely to succeed. Simultaneous targeting of different neoplastic cell populations within the same tumour may, therefore, prove of value. Neuron-glia 2 (NG2), a transmembrane chondroitin sulphateproteoglycan, present on developing glial cells, and GD3A, a gangliosideexpressed on developing migratory glia, are re-expressed in GBM. Materials and Methods: The aims of this study were to conduct ‘proof of concept’ experiments in human GBM cell lines to show that proliferative high NG2-expressing cells and high GD3A -expressing migratory cells could be effectively ablated using a Mab-Zap saporin immunotoxinsystem. Results: The combinatorial ablation of both NG2 and GD3A-expressing cells resulted in significant reduction in GBM cell viability compared to single epitope targeting and controls (p<0.0001); non-neoplastic astrocytes were not affected. Conclusion: Multiple targeting of GBM sub-populations may, therefore, help inform novel therapeutic approaches.