PMID- 16399226 OWN - NLM STAT- MEDLINE DCOM- 20060309 LR - 20111117 IS - 0304-3835 (Print) IS - 0304-3835 (Linking) VI - 231 IP - 2 DP - 2006 Jan 18 TI - The effect of a therapeutic dendritic cell-based cancer vaccination depends on the blockage of CTLA-4 signaling. PG - 247-56 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. FAU - Met, Ozcan AU - Met O AD - Department of Medical Anatomy, The Panum Institute, The University of Copenhagen, Blegdamsvej 3, Copenhagen 2200N, Denmark. ome@mai.ku.dk FAU - Wang, Mingjun AU - Wang M FAU - Pedersen, Anders E AU - Pedersen AE FAU - Nissen, Mogens H AU - Nissen MH FAU - Buus, Soren AU - Buus S FAU - Claesson, Mogens H AU - Claesson MH LA - eng PT - Journal Article PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation) RN - 0 (CTLA-4 Antigen) RN - 0 (Cancer Vaccines) RN - 0 (Ctla4 protein, mouse) RN - 0 (Egg Proteins) RN - 0 (Epitopes) RN - 0 (H-2 Antigens) RN - 0 (H-2Kb protein, mouse) RN - 0 (OVA-8) RN - 0 (Peptide Fragments) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Animals MH - Antibodies, Monoclonal/pharmacology MH - Antigens, CD MH - Antigens, Differentiation/*immunology MH - Bone Marrow/immunology MH - CTLA-4 Antigen MH - Cancer Vaccines/*therapeutic use MH - Dendritic Cells/*immunology MH - Drug Therapy, Combination MH - Egg Proteins/immunology MH - Epitopes/immunology MH - Female MH - H-2 Antigens/metabolism MH - Lymphoma/*drug therapy/immunology MH - Mice MH - Mice, Inbred C57BL MH - Ovalbumin/immunology MH - Peptide Fragments/immunology/*therapeutic use MH - Signal Transduction MH - Spleen/immunology MH - T-Lymphocytes, Cytotoxic/drug effects/immunology MH - Thymoma/*drug therapy/immunology MH - Transgenes/physiology MH - Vaccination EDAT- 2006/01/10 09:00 MHDA- 2006/03/10 09:00 CRDT- 2006/01/10 09:00 PHST- 2005/01/10 00:00 [received] PHST- 2005/02/01 00:00 [revised] PHST- 2005/02/04 00:00 [accepted] PHST- 2006/01/10 09:00 [pubmed] PHST- 2006/03/10 09:00 [medline] PHST- 2006/01/10 09:00 [entrez] AID - S0304-3835(05)00097-2 [pii] AID - 10.1016/j.canlet.2005.02.005 [doi] PST - ppublish SO - Cancer Lett. 2006 Jan 18;231(2):247-56. doi: 10.1016/j.canlet.2005.02.005.