Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma.
OBJECTIVE
Dendritic cells (DCs) are specialized cells of the immune system that are capable of generating potent immune responses that are active even within the "immunologically privileged" central nervous system. However, immune responses generated by DCs have also been demonstrated to produce clinically significant autoimmunity. Targeting the epidermal growth factor receptor variant III (EGFRvIII), which is a mutation specific to tumor tissue, could eliminate this risk. The purpose of this study was to demonstrate that DC-based immunizations directed solely against this tumor-specific antigen, which is commonly found on tumors that originate within or metastasize to the brain, could be efficacious.


METHODS
C3H mice were vaccinated with DCs mixed with a keyhole limpet hemocyanin conjugate of the tumor-specific peptide, PEP-3, which spans the EGFRvIII mutation, or the random-sequence peptide, PEP-1, and were intracerebrally challenged with a syngeneic melanoma expressing a murine homologue of EGFRvIII.


RESULTS
Systemic immunization with DCs mixed with PEP-3-keyhole limpet hemocyanin generated antigen-specific immunity. Among mice challenged with intracerebral tumors, this resulted in an approximately 600% increase in the median survival time (>300 d, P < 0.0016), relative to control values. Sixty-three percent of mice treated with DCs mixed with the tumor-specific peptide survived in the long term and 100% survived rechallenge with tumor, indicating that antitumor immunological memory was also induced.


CONCLUSIONS
In a murine melanoma model, immunization with DCs mixed with tumor-specific peptide results in an antigen-specific immunological response that recognizes the EGFRvIII mutation, has potent antitumor efficacy against intracerebral tumors that express EGFRvIII, and results in long-lasting antitumor immunity.
Heimberger
Amy B
AB
Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Archer
Gary E
GE
Crotty
Laura E
LE
McLendon
Roger E
RE
Friedman
Allan H
AH
Friedman
Henry S
HS
Bigner
Darell D
DD
Sampson
John H
JH
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology*; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D009154:Mutation; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology*
D019496:Cancer Vaccines; D000939:Epitopes; D022223:Vaccines, Subunit; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors