Electrofusion of syngeneic dendritic cells and tumor generates potent therapeutic vaccine

Cell Immunol. 2003 Oct;225(2):65-74. doi: 10.1016/j.cellimm.2003.09.005.

Abstract

Antigen presentation by dendritic cells (DCs) has the potential to elicit therapeutic immune responses against malignant tumors. One strategy utilizing DC-tumor fusion hybrids as cancer vaccine is particularly attractive because of polyclonal presentation of a diverse array of unaltered tumor antigens. We have recently developed a large-scale electrofusion technique for generating DC-tumor heterokaryons and demonstrated their superb immunogenicity. Here, employing the weakly immunogenic MCA205 sarcoma, a single vaccination with electrofusion hybrids eradicated tumors established in the lung, skin, and brain. Immunotherapy required intra-lymphoid vaccine delivery and co-administration of adjuvants such as OX-40R antibody. Tumor eradication was immunologically specific and involved the participation of both CD4 and CD8 T cells. Consistent with DC's functionality of MHC-restriction, the use of syngeneic DCs for fusion was an obligatory requirement. Fusion with allogeneic DCs completely lacked therapeutic effects. These findings provide a strong impetus for treating cancer patients with similarly generated DC-tumor hybrids.

Publication types

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

MeSH terms

  • Animals
  • Brain Neoplasms / immunology
  • Brain Neoplasms / therapy*
  • Cancer Vaccines*
  • Cell Fusion
  • Cell Transplantation
  • Dendritic Cells / immunology*
  • Immunotherapy, Active*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasm Metastasis / immunology
  • Neoplasm Metastasis / therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / therapy*
  • Tumor Cells, Cultured

Substances

  • Cancer Vaccines