Specific targeting of a mutant, activated FGF receptor found in glioblastoma using a monoclonal antibody.
A truncated epidermal growth factor receptor (EGFR) expressed from a rearranged and amplified EGFR gene is present at high frequency in gliomas. In this work we show that when this receptor is expressed in NIH3T3 fibroblasts it is partially activated and confers tumorigenicity to this cell line in vivo but no growth advantage in in vitro anchorage-independent growth assays. Because the mutation occurs in the extracellular domain of the receptor, it can be considered to represent a glioma-specific tumour marker. Here we demonstrate that 2 monoclonal antibodies, DH1.1 and DH8.3, raised to a synthetic peptide spanning the unique junctional sequence, can recognise the mutant receptor but not the normal receptor in both denatured and native states. Furthermore, radiolabelled antibody DH8.3 successfully targets tumours expressing this antigen in nude mice.
Hills
D
D
Imperial Cancer Research Fund Oncology Unit, Hammersmith Hospital, London, UK.
Rowlinson-Busza
G
G
Gullick
W J
WJ
D016475:3T3 Cells / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics; D000918:Antibody Specificity; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009154:Mutation; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011817:Rabbits; D014162:Transfection
D000911:Antibodies, Monoclonal; D000939:Epitopes; D066246:ErbB Receptors