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A novel adenovirus expressing human 4-1BB ligand enhances antitumor immunity.
Cancer Immunol Immunother. 2003 Feb; 52(2):97-106.CI

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-MUC1xanti-CD3). Cocultivation of Ad4-1BBL-infected tumor cells with either T-LAK cells or PBMC resulted in significant elevation of interferon-gamma (IFN-gamma), 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.

Authors+Show Affiliations

Department of Surgery, Division of Gastroenterological Surgery, Tohoku University Graduate School of Medicine, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12594573

Citation

Yoshida, Hiroshi, et al. "A Novel Adenovirus Expressing Human 4-1BB Ligand Enhances Antitumor Immunity." Cancer Immunology, Immunotherapy : CII, vol. 52, no. 2, 2003, pp. 97-106.
Yoshida H, Katayose Y, Unno M, et al. A novel adenovirus expressing human 4-1BB ligand enhances antitumor immunity. Cancer Immunol Immunother. 2003;52(2):97-106.
Yoshida, H., Katayose, Y., Unno, M., Suzuki, M., Kodama, H., Takemura, S., Asano, R., Hayashi, H., Yamamoto, K., Matsuno, S., & Kudo, T. (2003). A novel adenovirus expressing human 4-1BB ligand enhances antitumor immunity. Cancer Immunology, Immunotherapy : CII, 52(2), 97-106.
Yoshida H, et al. A Novel Adenovirus Expressing Human 4-1BB Ligand Enhances Antitumor Immunity. Cancer Immunol Immunother. 2003;52(2):97-106. PubMed PMID: 12594573.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel adenovirus expressing human 4-1BB ligand enhances antitumor immunity. AU - Yoshida,Hiroshi, AU - Katayose,Yu, AU - Unno,Michiaki, AU - Suzuki,Masanori, AU - Kodama,Hideaki, AU - Takemura,Shin-ichi, AU - Asano,Ryutaro, AU - Hayashi,Hiroki, AU - Yamamoto,Kuniharu, AU - Matsuno,Seiki, AU - Kudo,Toshio, Y1 - 2003/01/18/ PY - 2002/06/20/received PY - 2002/08/30/accepted PY - 2003/2/21/pubmed PY - 2003/4/4/medline PY - 2003/2/21/entrez SP - 97 EP - 106 JF - Cancer immunology, immunotherapy : CII JO - Cancer Immunol. Immunother. VL - 52 IS - 2 N2 - 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-MUC1xanti-CD3). Cocultivation of Ad4-1BBL-infected tumor cells with either T-LAK cells or PBMC resulted in significant elevation of interferon-gamma (IFN-gamma), 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. SN - 0340-7004 UR - https://www.unboundmedicine.com/medline/citation/12594573/A_novel_adenovirus_expressing_human_4_1BB_ligand_enhances_antitumor_immunity_ L2 - https://dx.doi.org/10.1007/s00262-002-0334-y DB - PRIME DP - Unbound Medicine ER -