Therapeutic anti-tumor response induced with epitope-pulsed fibroblasts genetically engineered for B7.1 Expression and IFN-γ secretion

Tae Sung Kim, Su W. Chung, Seung H. Kim, So N. Kang, Bok Y. Kang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Mouse fibroblasts (H-2(b)) were genetically engineered to express a co- stimulatory B7.1 and an IFN-γ (Fb/IFN-γ/B7.1). The Fb/IFN-γ/B7.1 cells were then pulsed with an ovalbumin epitope (amino acids 257-264, SIINFEKL, H- 2K(b)-restricted) as a model antigen (Fb/IFN-γ/B7.1/OVA) and tested for the induction of OVA-specific cytotoxic T lymphocytes (CTLs) in C57BL/6 mice (H- 2(b)). Genetically engineered fibroblasts lacking either IFN-γ or B7.1 were constructed and used as controls. Immunization with the Fb/IFN-γ/B7.1/OVA cells induced strong cytotoxic activity against OVA-expressing EL4 (EG7) tumor cells but not against other H-2(b) tumor cells, such as EL4, C1498, and B16F1. The magnitude of the cytotoxic response in mice with the Fb/IFN- γ/B7.1/OVA cells was significantly higher than that in mice immunized with any other cell construct. CD8+ T cells with OVA-specific cytotoxic activity were predominant in mice immunized with Fb/IFN-γ/B7.1/OVA cells. Furthermore, treatment with Fb/IFN-γ/B7.1/OVA cells significantly prolonged the survival period of EG7 tumor-bearing mice. Anti-tumor CTL immunity by the Fb/IFN-γ/B7.1/OVA cells could be induced without the help of host antigen- presenting cells, CD4+ T cells, or NK1.1+ cells. Our results suggest that fibroblasts can be genetically modified into efficient antigen-presenting cells for the induction of antigen-specific CTL response in cancer immunotherapy. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)427-433
Number of pages7
JournalInternational Journal of Cancer
Volume87
Issue number3
DOIs
Publication statusPublished - 2000 Aug 1
Externally publishedYes

Fingerprint

Epitopes
Fibroblasts
Neoplasms
Cytotoxic T-Lymphocytes
Therapeutics
Antigen-Presenting Cells
T-Lymphocytes
Antigens
Ovalbumin
Inbred C57BL Mouse
Immunotherapy
Immunity
Immunization
Amino Acids

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Therapeutic anti-tumor response induced with epitope-pulsed fibroblasts genetically engineered for B7.1 Expression and IFN-γ secretion. / Kim, Tae Sung; Chung, Su W.; Kim, Seung H.; Kang, So N.; Kang, Bok Y.

In: International Journal of Cancer, Vol. 87, No. 3, 01.08.2000, p. 427-433.

Research output: Contribution to journalArticle

@article{ac6e7944ead54a6597fffce90b207771,
title = "Therapeutic anti-tumor response induced with epitope-pulsed fibroblasts genetically engineered for B7.1 Expression and IFN-γ secretion",
abstract = "Mouse fibroblasts (H-2(b)) were genetically engineered to express a co- stimulatory B7.1 and an IFN-γ (Fb/IFN-γ/B7.1). The Fb/IFN-γ/B7.1 cells were then pulsed with an ovalbumin epitope (amino acids 257-264, SIINFEKL, H- 2K(b)-restricted) as a model antigen (Fb/IFN-γ/B7.1/OVA) and tested for the induction of OVA-specific cytotoxic T lymphocytes (CTLs) in C57BL/6 mice (H- 2(b)). Genetically engineered fibroblasts lacking either IFN-γ or B7.1 were constructed and used as controls. Immunization with the Fb/IFN-γ/B7.1/OVA cells induced strong cytotoxic activity against OVA-expressing EL4 (EG7) tumor cells but not against other H-2(b) tumor cells, such as EL4, C1498, and B16F1. The magnitude of the cytotoxic response in mice with the Fb/IFN- γ/B7.1/OVA cells was significantly higher than that in mice immunized with any other cell construct. CD8+ T cells with OVA-specific cytotoxic activity were predominant in mice immunized with Fb/IFN-γ/B7.1/OVA cells. Furthermore, treatment with Fb/IFN-γ/B7.1/OVA cells significantly prolonged the survival period of EG7 tumor-bearing mice. Anti-tumor CTL immunity by the Fb/IFN-γ/B7.1/OVA cells could be induced without the help of host antigen- presenting cells, CD4+ T cells, or NK1.1+ cells. Our results suggest that fibroblasts can be genetically modified into efficient antigen-presenting cells for the induction of antigen-specific CTL response in cancer immunotherapy. (C) 2000 Wiley-Liss, Inc.",
author = "Kim, {Tae Sung} and Chung, {Su W.} and Kim, {Seung H.} and Kang, {So N.} and Kang, {Bok Y.}",
year = "2000",
month = "8",
day = "1",
doi = "10.1002/1097-0215(20000801)87:3<427::AID-IJC18>3.0.CO;2-J",
language = "English",
volume = "87",
pages = "427--433",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Therapeutic anti-tumor response induced with epitope-pulsed fibroblasts genetically engineered for B7.1 Expression and IFN-γ secretion

AU - Kim, Tae Sung

AU - Chung, Su W.

AU - Kim, Seung H.

AU - Kang, So N.

AU - Kang, Bok Y.

PY - 2000/8/1

Y1 - 2000/8/1

N2 - Mouse fibroblasts (H-2(b)) were genetically engineered to express a co- stimulatory B7.1 and an IFN-γ (Fb/IFN-γ/B7.1). The Fb/IFN-γ/B7.1 cells were then pulsed with an ovalbumin epitope (amino acids 257-264, SIINFEKL, H- 2K(b)-restricted) as a model antigen (Fb/IFN-γ/B7.1/OVA) and tested for the induction of OVA-specific cytotoxic T lymphocytes (CTLs) in C57BL/6 mice (H- 2(b)). Genetically engineered fibroblasts lacking either IFN-γ or B7.1 were constructed and used as controls. Immunization with the Fb/IFN-γ/B7.1/OVA cells induced strong cytotoxic activity against OVA-expressing EL4 (EG7) tumor cells but not against other H-2(b) tumor cells, such as EL4, C1498, and B16F1. The magnitude of the cytotoxic response in mice with the Fb/IFN- γ/B7.1/OVA cells was significantly higher than that in mice immunized with any other cell construct. CD8+ T cells with OVA-specific cytotoxic activity were predominant in mice immunized with Fb/IFN-γ/B7.1/OVA cells. Furthermore, treatment with Fb/IFN-γ/B7.1/OVA cells significantly prolonged the survival period of EG7 tumor-bearing mice. Anti-tumor CTL immunity by the Fb/IFN-γ/B7.1/OVA cells could be induced without the help of host antigen- presenting cells, CD4+ T cells, or NK1.1+ cells. Our results suggest that fibroblasts can be genetically modified into efficient antigen-presenting cells for the induction of antigen-specific CTL response in cancer immunotherapy. (C) 2000 Wiley-Liss, Inc.

AB - Mouse fibroblasts (H-2(b)) were genetically engineered to express a co- stimulatory B7.1 and an IFN-γ (Fb/IFN-γ/B7.1). The Fb/IFN-γ/B7.1 cells were then pulsed with an ovalbumin epitope (amino acids 257-264, SIINFEKL, H- 2K(b)-restricted) as a model antigen (Fb/IFN-γ/B7.1/OVA) and tested for the induction of OVA-specific cytotoxic T lymphocytes (CTLs) in C57BL/6 mice (H- 2(b)). Genetically engineered fibroblasts lacking either IFN-γ or B7.1 were constructed and used as controls. Immunization with the Fb/IFN-γ/B7.1/OVA cells induced strong cytotoxic activity against OVA-expressing EL4 (EG7) tumor cells but not against other H-2(b) tumor cells, such as EL4, C1498, and B16F1. The magnitude of the cytotoxic response in mice with the Fb/IFN- γ/B7.1/OVA cells was significantly higher than that in mice immunized with any other cell construct. CD8+ T cells with OVA-specific cytotoxic activity were predominant in mice immunized with Fb/IFN-γ/B7.1/OVA cells. Furthermore, treatment with Fb/IFN-γ/B7.1/OVA cells significantly prolonged the survival period of EG7 tumor-bearing mice. Anti-tumor CTL immunity by the Fb/IFN-γ/B7.1/OVA cells could be induced without the help of host antigen- presenting cells, CD4+ T cells, or NK1.1+ cells. Our results suggest that fibroblasts can be genetically modified into efficient antigen-presenting cells for the induction of antigen-specific CTL response in cancer immunotherapy. (C) 2000 Wiley-Liss, Inc.

UR - http://www.scopus.com/inward/record.url?scp=0034256083&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034256083&partnerID=8YFLogxK

U2 - 10.1002/1097-0215(20000801)87:3<427::AID-IJC18>3.0.CO;2-J

DO - 10.1002/1097-0215(20000801)87:3<427::AID-IJC18>3.0.CO;2-J

M3 - Article

C2 - 10897050

AN - SCOPUS:0034256083

VL - 87

SP - 427

EP - 433

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 3

ER -