Adenovirus Vector-Mediated<b><i>in Vivo</i></b>Gene Transfer of OX40 Ligand to Tumor Cells Enhances Antitumor Immunity of Tumor-Bearing Hosts

Andarini, Sita; Kikuchi, Toshiaki; Nukiwa, Mio; Pradono, Prasenohadi; Suzuki, Takuji; Ohkouchi, Shinya; Inoue, Akira; Maemondo, Makoto; Ishii, Naoto; Saijo, Yasuo; Sugamura, Kazuo; Nukiwa, Toshihiro

doi:10.1158/0008-5472.can-03-3911

Cited by 83 publications

(59 citation statements)

References 41 publications

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“…This outcome is consistent with data in other systems demonstrating the enhancement of the CD8 ϩ T cell response to exogenous Ags by OX40 costimulation (20,21). Similarly, studies have shown that OX40 costimulation, given in the absence of tumor-targeted vaccination, augments antitumor immunity to poorly immunogenic tumors or tumors expressing model Ags (13)(14)(15)(16)18). In tumor-bearing FVB mice, we also observed anti-OX40 mediated enhancement of the antitumor immune response in mice given a control vaccine.…”

Section: Discussionsupporting

confidence: 91%

“…OX40-mediated costimulation has also been shown to prevent and even overcome established peptide-specific CD4 ϩ T cell tolerance (11,12). The provision of OX40 costimulation, through inoculation of OX40 ligand-expressing tumor cells (13,14), in vivo tumor cell transduction (15), or by systemic administration of OX40 ligand-fusion protein or anti-OX40 agonist Ab (16 -19), has been shown to enhance the immunogenicity of tumors in nontolerance model systems.…”

Section: Ox40 Costimulation Synergizes With Gm-csf Whole-cell Vaccinamentioning

confidence: 99%

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OX40 Costimulation Synergizes with GM-CSF Whole-Cell Vaccination to Overcome Established CD8+ T Cell Tolerance to an Endogenous Tumor Antigen

Murata

Ladle

Kim

et al. 2006

The Journal of Immunology

100

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T cell costimulation via OX40 is known to increase CD4+ T cell expansion and effector function and enhances the development of T cell memory. OX40 costimulation can also prevent, and even reverse, CD4+ T cell anergy. However, the role of OX40 in CD8+ T cell function is less well defined, particularly in the setting of immune tolerance. To determine the effects of OX40 costimulation on the induction of the host CD8+ T cell repertoire to an endogenous tumor Ag, we examined the fate of CD8+ T cells specific for the immunodominant rat HER-2/neu epitope, RNEU420–429, in FVB MMTV-neu (neu-N) mice, which express rat HER-2/neu protein in a predominantly mammary-restricted fashion. We show that the RNEU420–429-specific T cell repertoire in neu-N mice expands transiently after vaccination with a neu-targeted GM-CSF-secreting whole-cell vaccine, but quickly declines to an undetectable level. However, OX40 costimulation, when combined with GM-CSF-secreting tumor-targeted vaccination, can break established CD8+ T cell tolerance in vivo by enhancing the expansion, and prolonging the survival and effector function of CD8+ T cells specific for RNEU420–429. Moreover, we demonstrate that OX40 expression is up-regulated on both CD4+ and CD8+ T cells shortly after administration of a GM-CSF expressing vaccine. These studies highlight the increased efficacy of OX40 costimulation when combined with a GM-CSF-secreting vaccine, and define a new role for OX40 costimulation of CD8+ T cells in overcoming tolerance and boosting antitumor immunity.

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Section: Discussionsupporting

confidence: 91%

Section: Ox40 Costimulation Synergizes With Gm-csf Whole-cell Vaccinamentioning

confidence: 99%

OX40 Costimulation Synergizes with GM-CSF Whole-Cell Vaccination to Overcome Established CD8+ T Cell Tolerance to an Endogenous Tumor Antigen

Murata

Ladle

Kim

et al. 2006

The Journal of Immunology

100

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“…AdOX40L and AdNull are structurally similar replication-deficient recombinant Ads with E1 and E3 deletions in which the mouse OX40L gene and no transgene, respectively, are under control of the cytomegalovirus immediate-early promoter and enhancer (60,61). The propagation, purification, and titration of the Ad vectors were as previously described (62,63).…”

Section: Methodsmentioning

confidence: 99%

OX40 ligand expressed by DCs costimulates NKT and CD4+ Th cell antitumor immunity in mice

Zaini¹,

Andarini²,

Tahara³

et al. 2007

J. Clin. Invest.

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“…As previously described, the recombinant adenovirus vectors were propagated, purified by CsCl gradient centrifugation, and titrated by a serial-dilution end-point assay. Both vectors were free of replication-competent adenovirus (1,16).…”

Section: Methodsmentioning

confidence: 99%

Involvement of Fractalkine/CX3CL1 Expression by Dendritic Cells in the Enhancement of Host Immunity against Legionella pneumophila

et al. 2005

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Legionnaires' disease is clinically manifested as severe pneumonia caused by Legionella pneumophila. However, the dendritic cell (DC)-centered immunological framework of the host defense against L. pneumophila has not been fully delineated. For this study, we focused on a potent chemoattractant for lymphocytes, fractalkine/ CX3CL1, and observed that the fractalkine expression of DCs was somewhat up-regulated when they encountered L. pneumophila. We therefore hypothesized that fractalkine expressed by Legionella-capturing DCs is involved in the induction of T-cell-mediated immune responses against Legionella, which would be enhanced by a genetic modulation of DCs to overexpress fractalkine. In vivo immunization-challenge experiments demonstrated that DCs modified with a recombinant adenovirus vector to overexpress fractalkine (

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Adenovirus Vector-Mediatedin VivoGene Transfer of OX40 Ligand to Tumor Cells Enhances Antitumor Immunity of Tumor-Bearing Hosts

Cited by 83 publications

References 41 publications

OX40 Costimulation Synergizes with GM-CSF Whole-Cell Vaccination to Overcome Established CD8+ T Cell Tolerance to an Endogenous Tumor Antigen

OX40 Costimulation Synergizes with GM-CSF Whole-Cell Vaccination to Overcome Established CD8+ T Cell Tolerance to an Endogenous Tumor Antigen

OX40 ligand expressed by DCs costimulates NKT and CD4+ Th cell antitumor immunity in mice

Involvement of Fractalkine/CX3CL1 Expression by Dendritic Cells in the Enhancement of Host Immunity against Legionella pneumophila

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