Antigen-specific cytotoxicity and cell number of adoptively transferred T cells are efficiently maintained in vivo by re-stimulation with an antigen/interleukin-2 fusion protein

Bok Y. Kang, Young S. Lim, Su W. Chung, Eui J. Kim, Seung H. Kim, Seung Y. Hwang, Tae Sung Kim

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

In order to maintain in vivo anti-tumor efficacy of antigen (Ag)- specific T cells in adoptive immunotherapy for a prolonged period, we constructed a fusion protein (OVA/IL-2) containing ovalbumin (OVA) as a model tumor Ag, covalently linked to murine interleukin-2 (IL-2). The OVA/IL-2 protein produced in a baculovirus expression system displayed potent IL-2 bio-activity. Immunization with the OVA/IL-2 protein after adoptive transfer of OVA-specific T cells maintained the OVA-specific cytotoxicity and cell number of adoptively transferred T cells long term in vivo, while a simple mixture of recombinant OVA (rOVA) and rIL-2 did not. The response was dependent on the injection doses and times of the OVA/IL-2 protein. Furthermore, weekly re-stimulation of adoptively transferred OVA-specific T cells with the OVA/IL-2 protein cured 70% of tumor-bearing mice. In contrast, re-stimulation with a mixture of rOVA and rIL-2 could not significantly prolong the survival period of tumor-bearing mice. These studies suggest that the co-valent linkage between IL-2 and antigen confines the effect of IL-2 to antigen-specific T cells, leading to efficient maintenance of the anti-tumor activity of adoptively transferred T cells.

Original languageEnglish
Pages (from-to)569-573
Number of pages5
JournalInternational Journal of Cancer
Volume82
Issue number4
DOIs
Publication statusPublished - 1999 Aug 2
Externally publishedYes

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Ovalbumin
Interleukin-2
Cell Count
T-Lymphocytes
Antigens
Proteins
Neoplasm Antigens
Adoptive Immunotherapy
Neoplasms
Adoptive Transfer
Baculoviridae
Immunization
Maintenance
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Antigen-specific cytotoxicity and cell number of adoptively transferred T cells are efficiently maintained in vivo by re-stimulation with an antigen/interleukin-2 fusion protein. / Kang, Bok Y.; Lim, Young S.; Chung, Su W.; Kim, Eui J.; Kim, Seung H.; Hwang, Seung Y.; Kim, Tae Sung.

In: International Journal of Cancer, Vol. 82, No. 4, 02.08.1999, p. 569-573.

Research output: Contribution to journalArticle

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abstract = "In order to maintain in vivo anti-tumor efficacy of antigen (Ag)- specific T cells in adoptive immunotherapy for a prolonged period, we constructed a fusion protein (OVA/IL-2) containing ovalbumin (OVA) as a model tumor Ag, covalently linked to murine interleukin-2 (IL-2). The OVA/IL-2 protein produced in a baculovirus expression system displayed potent IL-2 bio-activity. Immunization with the OVA/IL-2 protein after adoptive transfer of OVA-specific T cells maintained the OVA-specific cytotoxicity and cell number of adoptively transferred T cells long term in vivo, while a simple mixture of recombinant OVA (rOVA) and rIL-2 did not. The response was dependent on the injection doses and times of the OVA/IL-2 protein. Furthermore, weekly re-stimulation of adoptively transferred OVA-specific T cells with the OVA/IL-2 protein cured 70{\%} of tumor-bearing mice. In contrast, re-stimulation with a mixture of rOVA and rIL-2 could not significantly prolong the survival period of tumor-bearing mice. These studies suggest that the co-valent linkage between IL-2 and antigen confines the effect of IL-2 to antigen-specific T cells, leading to efficient maintenance of the anti-tumor activity of adoptively transferred T cells.",
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