Antimetastatic vaccination against Lewis lung carcinoma with autologous tumor cells modified to express murine interleukin 12

Clin Exp Metastasis. 1998 Oct;16(7):623-32. doi: 10.1023/a:1006508413070.

Abstract

Interleukin 12 (IL-12) is a disulfide-linked heterodimer molecule produced predominantly by professional antigen presenting cells. It promotes the induction of sundry biological effects with significant relevance to antitumor immunity, such as enhancing a T(H)1 helper response, an in vivo antiangiogenic effect, induction of adhesion molecules that assist in lymphocyte homing to sites of tumor growth, and a direct stimulatory effect on both T-cells and NK cells. We tested the efficacy of an antimetastatic vaccine composed of autologous murine D122 cells transfected with both subunits of IL-12 cDNA to express biologically-active IL-12 molecule. Expression of IL-12 by D122 cells significantly reduced their tumorigenicity and metastatic potential in immunocompetent syngeneic hosts. Furthermore, vaccination of mice with 2 x 10(6) irradiated IL-12-transfected D122 cells engendered a protective CTL response which rejected a subsequent challenge with parental D122 cells and eradicated lung micrometastasis in animals whose primary tumors have been surgically removed. The antitumor effects of IL-12 were mediated primarily by its ability to induce gammaIFN expression in vivo. CD8+ T-cells as well as NK cells were crucial in the execution of the antitumor effects of IL-12. These results suggest that autologous tumor cells expressing IL-12 by gene transfer are a potent antitumor vaccine able to induce a systemic immune response against poorly immunogenic and spontaneously metastatic tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / therapeutic use*
  • Carcinoma, Lewis Lung / immunology
  • Carcinoma, Lewis Lung / prevention & control*
  • Carcinoma, Lewis Lung / secondary
  • Cell Division
  • Cells, Cultured
  • Genetic Therapy / methods*
  • Immunotherapy / methods
  • Interferon-gamma / genetics*
  • Interleukin-12 / genetics*
  • Interleukin-12 / immunology
  • Killer Cells, Natural / immunology
  • Mice
  • Neoplasm Metastasis / prevention & control*
  • Plasmids / genetics
  • Polymerase Chain Reaction
  • Th1 Cells / drug effects
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Cancer Vaccines
  • Interleukin-12
  • Interferon-gamma