Therapeutic immune response induced by electrofusion of dendritic and tumor cells

Cell Immunol. 2002 Nov;220(1):1-12. doi: 10.1016/s0008-8749(03)00009-1.

Abstract

To elicit a therapeutic antitumor immune response, dendritic cells (DCs) have been employed as a cellular adjuvant. Among various DC-based approaches, fusion of DCs and tumor cells potentially confers not only DC functionality, but also a continuous source of unaltered tumor antigens. We have recently demonstrated successful generation of fusion hybrids by a large-scale electrofusion technique. The immunogenicity and therapeutic potential of fusion hybrids were further analyzed in a model system of a murine melanoma cell line expressing beta-galactosidase (beta-gal) as a surrogate tumor antigen. A single vaccination with fusion hybrids plus IL-12 induced a therapeutic immune response against 3-day established pulmonary metastases. This immunotherapy was beta-gal specific and involved both CD4 and CD8 T cells. In vitro, fusion hybrids stimulated specific IFN-gamma secretion from both CD4 and CD8 immune T cells. They also nonspecifically induced IL-10 secretion from CD4 but not CD8 T cells. Compared to other DC loadings, our results demonstrate the superior immunogenicity of fusion. The current technique of electrofusion is adequately developed for clinical use in cancer immunotherapy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Fusion / instrumentation
  • Cell Fusion / methods*
  • Combined Modality Therapy
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Electric Stimulation
  • Female
  • Hybrid Cells / immunology*
  • Hybrid Cells / transplantation
  • Immunologic Factors / therapeutic use*
  • Immunotherapy / methods*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-12 / therapeutic use*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology
  • Lung Neoplasms / secondary*
  • Lung Neoplasms / therapy
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / secondary
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Specific Pathogen-Free Organisms
  • Vaccination*
  • beta-Galactosidase / genetics
  • beta-Galactosidase / immunology

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Immunologic Factors
  • Recombinant Fusion Proteins
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma
  • beta-Galactosidase