A novel adenovirus expressing human 4-1BB ligand enhances antitumor immunity

Hiroshi Yoshida, Yu Katayose, Michiaki Unno, Masanori Suzuki, Hideaki Kodama, Shin Ichi Takemura, Ryutaro Asano, Hiroki Hayashi, Kuniharu Yamamoto, Seiki Matsuno, Toshio Kudo

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

4-1BB ligand (4-1BBL), a member of the tumor necrosis factor (TNF) superfamily, interacts with 4-1BB (CDw137) expressed on activated T cells and delivers a costimulatory signal for T cell activation and growth. Various studies have demonstrated a role for murine 4-1BB in immune function, but relatively few investigations of human 4-1BB have been conducted. Here we report on the construction of a recombinant E1/E3-deleted adenovirus encoding human 4-1BBL (Ad4-1BBL) and its stimulation of antitumor immunity. Ad4-1BBL was able to efficiently infect several human adenocarcinoma cell lines and induce 4-1BBL expression on the cell surface within 24 h, this enhancing the antitumor activity not only of lymphokine-activated killer cells with a T cell phenotype (T-LAK) but also naive peripheral blood mononuclear cells (PBMC). This antitumor activity with T-LAK cells was further enhanced by addition of bispecific antibody (BsAb; anti-MUClxanti-CD3). Cocultivation of Ad4-1BBL-infected tumor cells with either T-LAK cells or PBMC resulted in significant elevation of interferon-gamma (IFN-γ), interleukin-2 (IL-2), and granulocyte-macrophage colony-stimulating factor (GM-CSF) production. Furthermore, remarkable tumor growth inhibition was observed in cholangiocarcinoma-grafted severe combined immunodeficient (SCID) mice to which Ad4-1BBL and T-LAK cells were administered when tumor size exceeded 5 mm in diameter. These results provide strong evidence in support of the efficacy of adenovirally delivered 4-1BBL for genetic immunotherapy of cancer.

Original languageEnglish
Pages (from-to)97-106
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume52
Issue number2
DOIs
Publication statusPublished - 2003 Feb 1
Externally publishedYes

Keywords

  • 4-1BB ligand
  • Adenovirus
  • Antitumor immunity
  • Cholangiocarcinoma
  • Costimulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'A novel adenovirus expressing human 4-1BB ligand enhances antitumor immunity'. Together they form a unique fingerprint.

Cite this