Genetically modified bone marrow-derived dendritic cells expressing tumor-associated viral or "self" antigens induce antitumor immunity in vivo

Eur J Immunol. 1997 Oct;27(10):2702-7. doi: 10.1002/eji.1830271033.


The clinical application of synthetic tumor peptide-based vaccines is currently limited to patients with specified major histocompatibility complex (MHC) class I alleles. Such logistic limitations may be overcome using tumor gene-based approaches. Here we describe the effective generation of dendritic cells (DC) expressing tumor peptide-MHC complexes as a result of particle-mediated transfer of genes encoding tumor-associated antigens (TAA). Bone marrow-derived DC were transfected with plasmid DNA encoding the tumor-associated viral antigen E7 derived from human papilloma virus (HPV) 16. When applied as a vaccine, these genetically modified DC induced antigen-specific CD8+ cytotoxic T lymphocytes (CTL) in vivo and promoted the rejection of a subsequent, normally lethal challenge with an HPV 16-transformed tumor cell line. Of greatest interest, immunization of mice with syngeneic DC genetically modified to enhance their presentation of a constitutive "self" epitope derived from the tumor-suppressor gene product p53 caused a significant reduction in the in vivo growth of a chemically induced p53-positive sarcoma. These results suggest that cancer vaccines consisting of DC genetically modified to express TAA of viral or "self" origin effectively induce antitumor immunity in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology*
  • Antigens, Viral / immunology*
  • Bone Marrow Cells / immunology*
  • Cancer Vaccines* / immunology
  • DNA, Recombinant / genetics
  • Dendritic Cells / immunology*
  • Epitopes / immunology*
  • Female
  • Gene Transfer Techniques
  • Genes, Reporter
  • H-2 Antigens / immunology
  • Humans
  • Immunization / methods*
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology*
  • Papillomavirus E7 Proteins
  • Sarcoma, Experimental / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection
  • Tumor Suppressor Protein p53 / immunology*


  • Antigens, Neoplasm
  • Antigens, Viral
  • Cancer Vaccines
  • DNA, Recombinant
  • Epitopes
  • H-2 Antigens
  • H-2K(K) antigen
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Tumor Suppressor Protein p53
  • oncogene protein E7, Human papillomavirus type 16
  • Interferon-gamma