Dendritic cells pulsed or fused with AML cellular antigen provide comparable in vivo antitumor protective responses.
OBJECTIVE
To investigate whether syngeneic BM-derived DCs generated in vitro and fused with syngeneic C1498 tumor cells (murine AML line) could induce a better antitumor protective effect compared to similarly generated DCs pulsed with C1498 lysate with or without co-injection of a class B CpG oligodeoxynucleotide (CpG 7909) in vivo.


METHODS
DCs were pulsed with C1498 lysate prior to intravenous administration 14 and 7 days prior to tumor challenge. Separate cohorts received DCs electrically fused to irradiated C1498 cells. Cohorts were administered DCs that were lysate-pulsed or fused with tumor cells on days 14 and 7 prior to tumor injection. Some cohorts were co-injected with CpG 7909 at the time of DC administration.


RESULTS
All DC vaccines significantly improved survival (p < 0.01) vs nonvaccinated controls. There was no difference in the antitumor protective response between mice that received pulsed vs fused DCs (47% vs 45% survival). Both DC vaccines generated a fivefold increase in splenic tumor-reactive cytotoxic T-lymphocyte precursor cells and significantly (p < 0.05) higher mean frequencies of IFN-gamma-producing splenocytes compared to controls. CpG 7909 improved the survival of mice receiving the fused DCs (p < 0.05) but not the pulsed DCs. Surviving mice were rechallenged and found to be resistant to lethal tumor injection.


CONCLUSIONS
DC vaccine strategies may be effective in generating anti-AML responses. No advantage was observed between lysate-pulsed and tumor cell-fused DCs. CpGs may provide an adjuvant effect depending on the type of DC vaccine administered.
Weigel
Brenda J
BJ
University of Minnesota Cancer Center and Department of Pediatrics, Division of Pediatric Hematology/Oncology and Blood and Marrow Transplant, Minneapolis, MN 55455, USA. weige007@umn.edu
Panoskaltsis-Mortari
Angela
A
Diers
Miechaleen
M
Garcia
Melissa
M
Lees
Chris
C
Krieg
Arthur M
AM
Chen
Wei
W
Blazar
Bruce R
BR
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002474:Cell-Free System / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D009368:Neoplasm Transplantation / Q000276:immunology / Q000379:methods; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000494:pharmacology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D009838:Oligodeoxyribonucleotides; C483020:ProMune; D007371:Interferon-gamma