Induction of antitumor immunity by transduction of CD40 ligand gene and interferon-γ gene into lung cancer

Masahiro Noguchi, Kazuyoshi Imaizumi, Tsutomu Kawabe, Hisashi Wakayama, Yoshitsugu Horio, Yoshitaka Sekido, Toru Hara, Naozumi Hashimoto, Masahide Takahashi, Kaoru Shimokata, Yoshinori Hasegawa

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

CD40-CD40 ligand (CD40L) interaction is an important costimulatory signaling pathway in the crosstalk between T cells and antigen-presenting cells. This receptor-ligand system is known to be essential in eliciting strong cellular immunity. Here we demonstrate that murine lung cancer cells (3LLSA) transduced with the CD40L gene (3LLSA-CD40L) were rejected in syngeneic C57BL/6 mice, but grew in CD40-deficient mice to the same extent as control tumor cells. Immunohistochemical study showed that inflammatory cells, including CD4+, CD8+ T cells and NK cells, infiltrated into the inoculated 3LLSA-CD40L tumor tissue. Inoculation of 3LLSA-CD40L cells into mice resulted in the induction of 3LLSA-specific cytotoxic T-cell immunity, and the growth of parental 3LLSA tumors was inhibited when 3LLSA cells were inoculated into C57BL/6 mice mixed with 3LLSA-CD40L cells or when they were rechallenged 4 weeks after 3LLSA-CD40L cells were rejected. Furthermore, co-inoculation of interferon (IFN)-γ-transduced cells (3LLSA-IFNγ) with 3LLSA-CD40L cells enhanced the antitumor immunity efficiently in vivo. These results indicate that the in vivo priming with CD40L- and IFN-γ gene-transduced lung cancer cells is a promising strategy for inducing antitumor immunity in the treatment of lung cancer.

Original languageEnglish
Pages (from-to)421-429
Number of pages9
JournalCancer Gene Therapy
Volume8
Issue number6
DOIs
Publication statusPublished - 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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