The effect of a therapeutic dendritic cell-based cancer vaccination depends on the blockage of CTLA-4 signaling

Cancer Lett. 2006 Jan 18;231(2):247-56. doi: 10.1016/j.canlet.2005.02.005.


Dendritic cells (DCs) were pulsed with the H-2K(b) binding OVA(257-264)-peptide (SIINFEKL), and used as one single-injection vaccine in combination with anti-CTLA-4 monoclonal antibody (mAb) to treat mice inoculated 3 days previously with 3x10(5) E.G7-OVA lymphoma cells. Neither DC vaccination nor CTLA-4 blockage alone prevented tumor growth in tumor challenged mice. In contrast, the combination of one vaccination and injection of anti-CTLA-4 mAb lead to rejection or retarded tumor growth in more than 60% of the mice. The OVA-transgene or the SIINFEKL-epitope was not lost in the progressing tumors of vaccinated mice, however, the highest degree of anti-SIINFEKL reactivity of host CTLs in an IFN-gamma ELISPOT assay was found only in mice showing complete tumor rejection. Vaccinated mice having rejected E.G7-OVA tumors were capable of rejecting subsequent challenges with 1x10(6) E.G7-OVA tumor cells, and later on these mice even rejected wild-type EL-4 tumor cells indicating that tumor epitope spreading takes place during the process of vaccination-induced E.G7-OVA rejection. In agreement with these observations, mice having rejected E.G7-OVA tumors showed long lasting CTL memory in spleen and bone marrow towards both the SIINFEKL-peptide and other EL-4-derived tumor rejecting epitopes.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD
  • Antigens, Differentiation / immunology*
  • Bone Marrow / immunology
  • CTLA-4 Antigen
  • Cancer Vaccines / therapeutic use*
  • Dendritic Cells / immunology*
  • Drug Therapy, Combination
  • Egg Proteins / immunology
  • Epitopes / immunology
  • Female
  • H-2 Antigens / metabolism
  • Lymphoma / drug therapy*
  • Lymphoma / immunology
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin / immunology
  • Peptide Fragments / immunology
  • Peptide Fragments / therapeutic use*
  • Signal Transduction
  • Spleen / immunology
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • Thymoma / drug therapy*
  • Thymoma / immunology
  • Transgenes / physiology
  • Vaccination


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • Cancer Vaccines
  • Ctla4 protein, mouse
  • Egg Proteins
  • Epitopes
  • H-2 Antigens
  • H-2Kb protein, mouse
  • OVA-8
  • Peptide Fragments
  • Ovalbumin