In vitro and in vivo antitumor properties of a T-cell clone generated from murine tumor-infiltrating lymphocytes

Bernard A. Fox, Paul J. Spiess, Attan Kasid, Raj Puri, James J. Mulé, Jeffrey S. Weber, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

Abstract

We have shown that a T-cell clone derived from murine tumorinfiltrating lymphocytes (TILs) can be established that mediates in vitro and in vivo antitumor effects. Utilizing this clone as a model, we examined the effect of cytokines on T-cell antitumor effector mechanisms in vitro and in vivo. This clone, termed BF-1, was generated by limiting dilution culture of a freshly excised MC-38 tumor, growing it in low levels of interleukin-2 (IL-2), and has been maintained for over 600 days. This clone became specifically cytotoxic for the MC-38 tumor during its first 100 days of culture. Pretreatment of the parental MC-38 tumor cell line with tumor necrosis factor (TNF) and interferon-γ (IFN-γ) increased its susceptibility to lysis by the BF-1 TIL line, but not to lysis by lymphokine-activated killer cells, in in vitro cytotoxicity assays. This increased susceptibility of the cytokine-pretreated targets was restricted to the parental tumor (MC-38), since similar pretreatment of MCA-102, MCA-105, or MCA-106 tumors did not render them susceptible to lysis by BF-1 TILs. This increased sensitivity to lysis in vitro was not the result of a change in the expression of major histocompatibility complex class I molecules. In experiments testing the ability of TILs to treat established lung metastases, the combination of TNF, IFN-γ, IL-2, and TILs was shown to increase significantly the antitumor properties of this therapy when compared to TILs and IL-2. This result demonstrates that combinations of lymphokines, which when administered alone do not affect micrometastatic tumor burdens (TNF, IFN-γ), can synergize with cellular immunotherapy in the treatment of established tumor burdens and may have applicabilities to the treatment of cancer in humans.

Original languageEnglish (US)
Pages (from-to)499-511
Number of pages13
JournalJournal of Biological Response Modifiers
Volume9
Issue number5
StatePublished - Oct 1990

Keywords

  • Immunotherapy
  • Interferon-γ
  • T-cell clones
  • Tumor necrosis factor
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Cancer Research

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