An EGFRvIII-targeted bispecific T-cell engager overcomes limitations of the standard of care for glioblastoma.
While advanced surgical techniques, radiation therapy and chemotherapeutic regimens provide a tangible benefit for patients with glioblastoma (GBM), the average survival from the time of diagnosis remains less than 15 months. Current therapy for GBM is limited by the nonspecific nature of treatment, prohibiting therapy that is aggressive and prolonged enough to eliminate all malignant cells. As an alternative, bispecific antibodies can redirect the immune system to eliminate malignant cells with exquisite potency and specificity. We have recently developed an EGF receptor variant III (EGFRvIII)-targeted bispecific antibody that redirects T cells to eliminate EGFRvIII-expressing GBM. The absolute tumor specificity of EGFRvIII and the lack of immunologic crossreactivity with healthy cells allow this therapeutic to overcome limitations associated with the nonspecific nature of the current standard of care for GBM. Evidence indicates that the molecule can exert therapeutically significant effects in the CNS following systemic administration. Additional advantages in terms of ease-of-production and off-the-shelf availability further the clinical utility of this class of therapeutics.
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. patrick.gedeon@duke.edu
Patrick C
PC
Gedeon
Bryan D
BD
Choi
Tiffany R
TR
Hodges
Duane A
DA
Mitchell
Darell D
DD
Bigner
John H
JH
Sampson
D000818:Animals; D018033:Antibodies, Bispecific / Q000378:metabolism / Q000627:therapeutic use*; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism; D005909:Glioblastoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D059039:Standard of Care; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
D018033:Antibodies, Bispecific; D000970:Antineoplastic Agents; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors