The immunotherapeutic effect of dendritic cells vaccine modified with interleukin-18 gene and tumor cell lysate on mice with pancreatic carcinoma

World J Gastroenterol. 2002 Oct;8(5):908-12. doi: 10.3748/wjg.v8.i5.908.

Abstract

Aim: To estimate the effect of a therapeutic vaccine against pancreatic carcinoma based on dendritic cell (DC) vaccine modified with tumor lysate and Interleukin-18 gene.

Methods: The BALB/C mice model of pancreatic carcinoma was induced with DMBA. DC vaccine was constructed through pulsed with tumor lysate and transfected by the recombinant adenoviral vector encoding IL-18 gene. The immunotherapeutic effects of DC vaccine on mice with pancreatic carcinoma were assessed (divided into DC-IL18-Lysate group, DC-Lysate group, DC-IL18 group, DC group, PBS group).

Results: After vaccination of the DC vaccine, the concentration of IL-18 and IFN-gamma were 2161+/-439 ng x L(-1) and 435+/-72 ng x L(-1) in DC-IL18-Lysate group and there was significant difference compared with other groups (P<0.01). After vaccination of the DC vaccine, the transplanted tumors were observed on 30 days in DC-Lysate groups, on 16 days in DC-IL18 groups, on 3 days in control group, but mice remained tumor-free for at least 50 days in DC-IL18-Lysate group and there was significant difference between DC-IL18-Lysate group and other groups (P<0.01). The median survival exceeds 62 days in DC-IL18-Lysate group. But the median survival was 48.6 days in DC-Lysate group, 33 days in DC-IL18 group, 17 days in PBS group. The survival period was obviously prolonged in DC-IL18-Lysate group than in other groups (P<0.05, P<0.01). The weight of pancreatic tumor was 0.22+/-0.083 g in DC-IL18-Lysate group, 1.45+/-0.74 g in DC-Lysate group, 1.89+/-1.34 g in DC-IL18 group, 3.0+/-1.6 g in DC group, 2.9+/-2.0 g in PBS group and the weight of tumor obviously reduced in DC-IL18-Lysate group than in other groups (P<0.05, P<0.01).

Conclusion: DC vaccine modified with tumor lysate and Interleukin-18 gene can induce a specific and effective immune response against pancreatic carcinoma cell.

MeSH terms

  • Animals
  • Cancer Vaccines / genetics*
  • Cancer Vaccines / pharmacology*
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Immunotherapy
  • Interferon-gamma / blood
  • Interleukin-18 / blood
  • Interleukin-18 / genetics*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / therapy*
  • Spleen / cytology
  • Tumor Cells, Cultured

Substances

  • Cancer Vaccines
  • Interleukin-18
  • Interferon-gamma