title: Dual targeting NG2 and GD3A using Mab-Zap immunotoxin results in reduced glioma cell viability in vitro.
abstract: 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 sulphate proteoglycan, present on developing glial cells, and GD3(A), a ganglioside expressed on developing migratory glia, are re-expressed in GBM.
  
  
  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 GD3(A) -expressing migratory cells could be effectively ablated using a Mab-Zap saporin immunotoxin system.
  
  
  RESULTS
  The combinatorial ablation of both NG2 and GD3(A)-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.
  
  
  CONCLUSIONS
  Multiple targeting of GBM sub-populations may, therefore, help inform novel therapeutic approaches.
authors.affiliation: Cellular and Molecular Neuro-oncology Research Group, Cellular and Molecular Medicine Research Division, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, U.K. samantha.higgins@port.ac.uk.
authors.forename: Samantha C
authors.initials: SC
authors.lastname: Higgins
authors.affiliation: Cellular and Molecular Neuro-oncology Research Group, Cellular and Molecular Medicine Research Division, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, U.K.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Fillmore
authors.affiliation: Department of Neurosurgery, King's College Hospital, London, U.K.
authors.forename: Keyoumars
authors.initials: K
authors.lastname: Ashkan
authors.affiliation: Cellular Neurophysiology Research Group, Cellular and Molecular Medicine Research Division, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, U.K.
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Butt
authors.affiliation: Cellular and Molecular Neuro-oncology Research Group, Cellular and Molecular Medicine Research Division, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, U.K.
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Pilkington
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005732:Gangliosides / Q000276:immunology / Q000378:metabolism; D005910:Glioma; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D011509:Proteoglycans / Q000276:immunology / Q000378:metabolism; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology*; D000076985:Saporins; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D000970:Antineoplastic Agents; D005732:Gangliosides; D000922:Immunotoxins; D011509:Proteoglycans; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D000099216:Chondroitin Sulfate Proteoglycan 4; C026226:ganglioside, GD3
keywords: GD3A; NG2 proteoglycan; glioma; immunoablation; saporin