EGFRvIII: an oncogene deletion mutant cell surface receptor target expressed by multiple tumour types

Optimal immunotherapeutic approaches to cancer cell eradication require the specific recognition of neoplastic cells and minimal destruction of bystander, normal cells. This is especially crucial within the CNS because of the infiltrative growth pattern of primary CNS tumours. The recently defined class III variant of the epidermal growth factor receptor (EGFRvIII), which is a transmembrane, tumour-specific, altered growth factor receptor molecule not expressed in normal tissues, shows promise in preclinical studies as a mediator of multiple immunotherapeutic approaches to tumours, both CNS and systemic, that express this marker. Specific monoclonal antibodies (mAbs) and derived constructs specific for EGFRvIII have been developed and the molecular engineering and affinity maturation techniques currently available have resulted in the generation of highly specific cytostatic and cytotoxic reagents for clinical trial. In addition, the immunogenic properties of the EGFRvIII transmembrane segment have made possible several successful vaccination strategies in preclinical models. In summary, targeting of the EGFRvIII molecule by a variety of immune approaches is a promising adjunct to current therapy.