Intracerebral delivery of a third generation EGFRvIII-specific chimeric antigen receptor is efficacious against human glioma

Bryan D Choi; Carter M Suryadevara; Patrick C Gedeon; James E Herndon 2nd; Luis Sanchez-Perez; Darell D Bigner; John H Sampson

doi:10.1016/j.jocn.2013.03.012

Intracerebral delivery of a third generation EGFRvIII-specific chimeric antigen receptor is efficacious against human glioma

J Clin Neurosci. 2014 Jan;21(1):189-90. doi: 10.1016/j.jocn.2013.03.012. Epub 2013 Sep 17.

Authors

Bryan D Choi¹, Carter M Suryadevara², Patrick C Gedeon³, James E Herndon 2nd⁴, Luis Sanchez-Perez², Darell D Bigner⁵, John H Sampson⁶

Affiliations

¹ Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Box 3050, Durham, NC 27710, USA; Department of Pathology, Duke University Medical Center, Durham, NC, USA.
² Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Box 3050, Durham, NC 27710, USA.
³ Department of Biomedical Engineering, Duke University, Durham, NC, USA.
⁴ Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
⁵ Department of Pathology, Duke University Medical Center, Durham, NC, USA; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
⁶ Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Box 3050, Durham, NC 27710, USA; Department of Pathology, Duke University Medical Center, Durham, NC, USA; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. Electronic address: john.sampson@duke.edu.

Abstract

Chimeric antigen receptors (CAR)-transduced T cells hold great promise in the treatment of malignant disease. Here, we demonstrate that intracerebral injection with a human, epidermal growth factor receptor variant III (EGFRvIII)-specific, third generation CAR successfully treats glioma in mice. Importantly, these results endorse clinical translation of this CAR in patients with EGFRvIII-expressing brain tumors.

Keywords: Central nervous system neoplasms; Epidermal growth factor receptor; Glioblastoma; Immunotherapy; T-lymphocytes.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Brain Neoplasms / immunology
Cell Line, Tumor
Chimera
ErbB Receptors / genetics
ErbB Receptors / immunology*
Glioma / immunology*
Humans
Immunotherapy / methods
Mice
Mice, Inbred NOD
Mice, SCID
Receptors, Antigen, T-Cell / immunology*
Transduction, Genetic
Xenograft Model Antitumor Assays

Substances

Receptors, Antigen, T-Cell
epidermal growth factor receptor VIII
ErbB Receptors

Abstract

Publication types

MeSH terms

Substances

Grants and funding