Dendritic cells pulsed or fused with AML cellular antigen provide comparable in vivo antitumor protective responses

Exp Hematol. 2006 Oct;34(10):1403-12. doi: 10.1016/j.exphem.2006.05.011.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Line, Tumor
  • Cell-Free System / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Dendritic Cells / transplantation*
  • Female
  • Interferon-gamma / immunology
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Mice
  • Neoplasm Transplantation / immunology
  • Neoplasm Transplantation / methods
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy
  • Oligodeoxyribonucleotides / immunology
  • Oligodeoxyribonucleotides / pharmacology
  • Spleen / immunology
  • Spleen / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Vaccination*

Substances

  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • CPG-oligonucleotide
  • Cancer Vaccines
  • Oligodeoxyribonucleotides
  • ProMune
  • Interferon-gamma