Genetically engineered fibroblasts with antigen-presenting capability: Efficient induction of an antigen-specific cytotoxic T-lymphocyte response and protection against tumor development in vivo

Tae S. Kim, Su W. Chung, Seung H. Kim, Bok Y. Kang, Seung Y. Hwang, Jae W. Lee

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

BLK mouse fibroblasts (H-2b) were genetically engineered to express costimulatory B7.1 and interleukin-2 (BLK/IL2/B7.1). The BLK/IL2/B7.1 cells were then pulsed with an ovalbumin (OVA) epitope as a model antigen (Ag) (BLK/IL2/B7.1/OVA), and tested for the induction of OVA-specific cytotoxic T lymphocytes (CTLs) in C57BL/6 mice (H-2b). The genetically engineered fibroblasts lacking one or two of three factors (interleukin-2, B7.1, and OVA) were constructed and used as controls. Immunization with the BLK/IL2/B7.1/OVA cells induced strong cytotoxic activities against OVA- expressing EL4 (EG7) tumor cells, but not against other H-2b tumor cells, such as EL4, C1498 and B16F1 cells. The magnitude of the cytotoxic response in mice with the BLK/IL2/B7.1/OVA cells was significantly higher than the response in mice immunized with any other cell constructs. CD8+ T cells with OVA-specific cytotoxic activities were predominant in mice immunized with the BLK/IL2/B7.1/OVA cells. Furthermore, immunization with the BLK/IL2/B7.1/OVA cells significantly prolonged the survival of mice, compared with any other cell constructs, when the mice were challenged with EG7 tumor cells at 2 weeks postimmunization. Induction of antitumoral CTL immunity by the BLK/IL2/B7.1/OVA cells was independent of host Ag-presenting cells and of CD4+ T-cell and natural killer 1.1+ cell help. These results suggest that fibroblasts can be genetically modified to efficient Ag-presenting cells for the induction of an Ag-specific CTL response.

Original languageEnglish (US)
Pages (from-to)861-869
Number of pages9
JournalCancer Gene Therapy
Volume7
Issue number6
DOIs
StatePublished - Jan 1 2000

Keywords

  • B7.1
  • Fibroblast
  • Gene therapy
  • Interleukin-2
  • Tumor immunology

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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