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Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma.

Publication ,  Journal Article
Heimberger, AB; Archer, GE; Crotty, LE; McLendon, RE; Friedman, AH; Friedman, HS; Bigner, DD; Sampson, JH
Published in: Neurosurgery
January 2002

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. CONCLUSION: 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.

Duke Scholars

Published In

Neurosurgery

DOI

ISSN

0148-396X

Publication Date

January 2002

Volume

50

Issue

1

Start / End Page

158 / 164

Location

United States

Related Subject Headings

  • Vaccines, Subunit
  • Tumor Cells, Cultured
  • Neurology & Neurosurgery
  • Neoplasm Transplantation
  • Mutation
  • Mice, Inbred C3H
  • Mice
  • Melanoma, Experimental
  • Male
  • ErbB Receptors
 

Citation

APA
Chicago
ICMJE
MLA
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Heimberger, A. B., Archer, G. E., Crotty, L. E., McLendon, R. E., Friedman, A. H., Friedman, H. S., … Sampson, J. H. (2002). Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma. Neurosurgery, 50(1), 158–164. https://doi.org/10.1097/00006123-200201000-00024
Heimberger, Amy B., Gary E. Archer, Laura E. Crotty, Roger E. McLendon, Allan H. Friedman, Henry S. Friedman, Darell D. Bigner, and John H. Sampson. “Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma.Neurosurgery 50, no. 1 (January 2002): 158–64. https://doi.org/10.1097/00006123-200201000-00024.
Heimberger AB, Archer GE, Crotty LE, McLendon RE, Friedman AH, Friedman HS, et al. Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma. Neurosurgery. 2002 Jan;50(1):158–64.
Heimberger, Amy B., et al. “Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma.Neurosurgery, vol. 50, no. 1, Jan. 2002, pp. 158–64. Pubmed, doi:10.1097/00006123-200201000-00024.
Heimberger AB, Archer GE, Crotty LE, McLendon RE, Friedman AH, Friedman HS, Bigner DD, Sampson JH. Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma. Neurosurgery. 2002 Jan;50(1):158–164.
Journal cover image

Published In

Neurosurgery

DOI

ISSN

0148-396X

Publication Date

January 2002

Volume

50

Issue

1

Start / End Page

158 / 164

Location

United States

Related Subject Headings

  • Vaccines, Subunit
  • Tumor Cells, Cultured
  • Neurology & Neurosurgery
  • Neoplasm Transplantation
  • Mutation
  • Mice, Inbred C3H
  • Mice
  • Melanoma, Experimental
  • Male
  • ErbB Receptors