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

Abstract

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.

• Authors: Ozcan Met, Mingjun Wang, Anders E Pedersen, Mogens H Nissen, Søren Buus, Mogens H Claesson
• Journal: Cancer letters (Cancer Lett) Vol. 231 Issue 2 Pg. 247-56 (Jan 18 2006) ISSN: 0304-3835 [Print] Ireland
• PMID: 16399226 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• 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, immunology)
• Mice
• Mice, Inbred C57BL
• Ovalbumin (immunology)
• Peptide Fragments (immunology, therapeutic use)
• Signal Transduction
• Spleen (immunology)
• T-Lymphocytes, Cytotoxic (drug effects, immunology)
• Thymoma (drug therapy, immunology)
• Transgenes (physiology)
• Vaccination