Antitumor Responses of Adoptively-Transferred Tumor-Specific T-Cell Cultures in a Murine Lymphoma Model

  • Kim, Hee-Sue (College of Pharmacy, Chungnam National University) ;
  • Lee, Hee-Gu (Molecular and Cellular Biology Research Group, Korea Research Institute of Bioscience & Biotechnology) ;
  • Lim, Jong-Seok (Molecular and Cellular Biology Research Group, Korea Research Institute of Bioscience & Biotechnology) ;
  • Lee, Ki-Young (Molecular and Cellular Biology Research Group, Korea Research Institute of Bioscience & Biotechnology) ;
  • Kim, Jae-Wha (Molecular and Cellular Biology Research Group, Korea Research Institute of Bioscience & Biotechnology) ;
  • Chung, Kyeong-Soo (College of Pharmacy, Chungnam National University) ;
  • Choe, Yong-Kyung (Molecular and Cellular Biology Research Group, Korea Research Institute of Bioscience & Biotechnology) ;
  • Choe, In-Seong (Molecular and Cellular Biology Research Group, Korea Research Institute of Bioscience & Biotechnology) ;
  • Chung, Tai-Wha (Molecular and Cellular Biology Research Group, Korea Research Institute of Bioscience & Biotechnology) ;
  • Kim, Kil-Hyoun (College of Pharmacy, Ewha Womans University)
  • Received : 1995.11.20
  • Published : 1995.11.30

Abstract

The purpose of this study was to establish an in vitro culture method of tumor-specific T cells, and determine the efficacy of the cultured tumor-specific cytotoxic T-lymphocytes (CTL) as an agent of anti-tumor immunotherapy against a murine lymphoma, TIMI.4. Tumor-specific T-lymphocytes derived from C57BL/6 mice (thy-1.2) immune to TIMI.4 were activated by in vitro stimulation with the irradiated TIMI.4 cells, and expanded by restimulation with TIMI.4 in the presence of the concanavalin A-stimulated rat spleen culture supernatant, and splenic antigen-presenting cells. In vitro restimulation enhanced markedly the proportion of $CD8^+$, a predominant surface marker of CTL and the cytotoxic activity in the cultured immune T cell population. The resulting TIMI.4-specific T cells were adoptively transferred into nude mice. The tumor cells residing in the host after 7 days of adoptive transfer to B6.PL (thy-1.1) mice were quantified by use of an antibody directed to the thy-1.2 allele. The TIMI.4 cells in the recipient nude mice were decreased in a dose-dependent manner. Anti-tumor activity of the TIMI.4-specific T cells was also demonstrated by a survival test, where the tumor-bearing nu/nu mice which received the activated T-cells survived about 30% longer than the control mice which received the tumor cells alone. These suggest that adoptive transfer of TIMI.4-specific T cells could be a candidate for effective therapy of the murine lymphoma.

Keywords

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