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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

BLK mouse fibroblasts (H-2 b) 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-2 b). 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-2 b 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
Pages (from-to)861-869
Number of pages9
JournalCancer Gene Therapy
Volume7
Issue number6
Publication statusPublished - 2000 Jul 17
Externally publishedYes

Fingerprint

Cytotoxic T-Lymphocytes
Ovalbumin
Fibroblasts
Interleukin-2
Antigens
Neoplasms
Antigen-Presenting Cells
Immunization
T-Lymphocytes
Inbred C57BL Mouse
Natural Killer Cells
Epitopes
Immunity

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Genetically engineered fibroblasts with antigen-presenting capability : Efficient induction of an antigen-specific cytotoxic T-lymphocyte response and protection against tumor development in vivo. / Kim, Tae Sung; Chung, Su W.; Kim, Seung H.; Kang, Bok Y.; Hwang, Seung Y.; Lee, Jae W.

In: Cancer Gene Therapy, Vol. 7, No. 6, 17.07.2000, p. 861-869.

Research output: Contribution to journalArticle

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abstract = "BLK mouse fibroblasts (H-2 b) 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-2 b). 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-2 b 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.",
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AU - Kim, Seung H.

AU - Kang, Bok Y.

AU - Hwang, Seung Y.

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