title: Antibody-based immunotherapy for malignant glioma.
abstract: Conventional therapy for malignant glioma (MG) fails to specifically eliminate tumor cells, resulting in toxicity that limits therapeutic efficacy. In contrast, antibody-based immunotherapy uses the immune system to eliminate tumor cells with exquisite specificity. Increased understanding of the pathobiology of MG and the profound immunosuppression present among patients with MG has revealed several biologic targets amenable to antibody-based immunotherapy. Novel antibody engineering techniques allow for the production of fully human antibodies or antibody fragments with vastly reduced antigen-binding dissociation constants, increasing safety when used clinically as therapeutics. In this report, we summarize the use of antibody-based immunotherapy for MG. Approaches currently under investigation include the use of antibodies or antibody fragments to: (1) redirect immune effector cells to target tumor mutations, (2) inhibit immunosuppressive signals and thereby stimulate an immunological response against tumor cells, and (3) provide costimulatory signals to evoke immunologic targeting of tumor cells. These approaches demonstrate highly compelling safety and efficacy for the treatment of MG, providing a viable adjunct to current standard-of-care therapy for MG.
authors.affiliation: Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC; Department of Biomedical Engineering, Duke University, Durham, NC; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC. Electronic address: patrick.gedeon@duke.edu.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Gedeon
authors.affiliation: Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC; Department of Biomedical Engineering, Duke University, Durham, NC; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Riccione
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Fecci
authors.affiliation: Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC; Department of Biomedical Engineering, Duke University, Durham, NC; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC.
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000235:genetics / Q000628:therapy*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D005910:Glioma / Q000235:genetics / Q000628:therapy*; D006801:Humans; D056747:Immunomodulation; D007167:Immunotherapy / Q000379:methods*; D058990:Molecular Targeted Therapy / Q000379:methods
chemical_list: D000906:Antibodies; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors