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

TY - JOUR

T1 - The effect of a therapeutic dendritic cell-based cancer vaccination depends on the blockage of CTLA-4 signaling.

AU - Met, Ozcan

AU - Wang, Mingjun

AU - Pedersen, Anders E

AU - Nissen, Mogens H

AU - Buus, Søren

AU - Claesson, Mogens H

N1 - Keywords: Animals; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation; Bone Marrow; Cancer Vaccines; Dendritic Cells; Drug Therapy, Combination; Egg Proteins; Epitopes; Female; H-2 Antigens; Lymphoma; Mice; Mice, Inbred C57BL; Ovalbumin; Peptide Fragments; Signal Transduction; Spleen; T-Lymphocytes, Cytotoxic; Thymoma; Transgenes; Vaccination

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.1016/j.canlet.2005.02.005

DO - 10.1016/j.canlet.2005.02.005

M3 - Journal article

C2 - 16399226

SN - 0304-3835

VL - 231

SP - 247

EP - 256

JO - Cancer Letters

JF - Cancer Letters

IS - 2

ER -