Intratumoral IL-18 gene transfer improves therapeutic efficacy of antibody-targeted superantigen in established murine melanoma

Wang, Q; Yu, Hongjun; Ju, Dian Wen; He, Liangmei; Pan, JP; Xia, D J; Zhang, L H; Cao, Xuetao

doi:10.1038/sj.gt.3301428

Cited by 30 publications

(26 citation statements)

References 44 publications

(48 reference statements)

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“…The recombinant adenovirus was released from 293 cells by three freeze-thaw cycles and subsequently propagated with 293 cells as previously described. 20 The adenoviral titers were determined by plaque-forming assay on 293 cells. Briefly, serial 10-fold dilutions of adenovirus were added to 24-well plates (Corning, New York, USA) containing confluent 293 cell monolayers.…”

Section: Preparation Of Recombinant Adenovirusesmentioning

confidence: 99%

Adenovirus-mediated LIGHT gene modification in murine B-cell lymphoma elicits a potent antitumor effect

Liu

et al. 2010

Cell Mol Immunol

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Here, we investigated the antitumor effect of adenovirus-mediated gene transfer of LIGHT, the tumor-necrosis factor (TNF) superfamily member also known as TNFSF14, in the murine A20 B-cell lymphoma. LIGHT gene modification resulted in upregulated expression of Fas and the accessory molecule-intercellular adhesion molecule-1 (ICAM-1) on A20 cells and led to enhanced A20 cell apoptosis. LIGHT-modified A20 cells effectively stimulated the proliferation of T lymphocytes and interferon (IFN)-c production in vitro. Immunization of BALB/c mice with a LIGHT-modified A20 cell vaccine efficiently elicited protective immunity against challenge with the parental tumor cell line. Adenovirus-mediated gene transfer of LIGHT by intratumoral injection exerted a very potent antitumor effect against pre-existing A20 cell lymphoma in BALB/c mice. This adenovirus-mediated LIGHT therapy induced substantial splenic natural killer (NK) and cytotoxic T lymphocyte (CTL) activity, enhanced tumor infiltration by inflammatory cells and increased chemokine expression of CC chemokine ligand 21 (CCL21), IFN-inducible protein-10 (IP-10) and monokine induced by IFN-c (Mig) from tumor tissues. Thus, adenovirus-mediated LIGHT therapy might have potential utility for the prevention and treatment of B-cell lymphoma.

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Section: Preparation Of Recombinant Adenovirusesmentioning

confidence: 99%

Adenovirus-mediated LIGHT gene modification in murine B-cell lymphoma elicits a potent antitumor effect

Liu

et al. 2010

Cell Mol Immunol

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“…7 Recently, several reports have shown that IL-18 has potent antitumor effects when administered in animal models of lung cancer, breast cancer, sarcoma and melanoma in vivo. [7][8][9][10][11] In these models, systemic administration of IL-18 9,12 or in vivo IL-18 gene transfer 13,14 inhibited tumor growth and prolonged the survival of tumor-bearing mice. The antitumor effects of IL-18 in multiple animal models provided the rationale for investigation of recombinant human (rh) IL-18 in clinic cancer immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Oncolytic adenovirus expressing interleukin-18 induces significant antitumor effects against melanoma in mice through inhibition of angiogenesis

Zheng

Park

et al. 2009

Cancer Gene Ther

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It has been shown that interleukin 18 (IL-18) exerts antitumor activity. In this study, we investigated whether oncolytic adenovirusmediated gene transfer of IL-18 could induce strong antitumor activity. A tumor-selective replicating adenovirus expressing IL-18 (ZD55-IL-18) was constructed by insertion of an IL-18 expression cassette into the ZD55 vector, which is based on deletion of the adenoviral E1B 55-kDa gene. It has been shown that ZD55-IL-18 exerted a strong cytopathic effect and significant apoptosis in tumor cells. ZD55-IL-18 significantly decreased vascular endothelial growth factor and CD34 expression in the melanoma cells. Treatment of established tumors with ZD55-IL-18 showed much stronger antitumor activity than that induced by ZD55-EGFP (enhanced green fluorescent protein) or Ad-IL-18. These data indicated that oncolytic adenovirus expressing IL-18 could exert potential antitumor activity through inhibition of angiogenesis and offer a novel approach to melanoma therapy.

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“…In vivo, the antitumor effects of IL-18 have been studied in a number of tumorbearing mouse models (31)(32)(33)(34)(35)(36). In these models, systemic administration of IL-18 (31-34) or in vivo IL-18 gene transfer (35,36) inhibited tumor growth and prolonged the survival of tumorbearing mice by mechanisms not precisely defined; nevertheless, at least in some models, these included involvement of NK and T cells (33,36). In a recent report, dendritic cells genetically modified to secrete IL-18 were found to promote antitumor activity in a mouse sarcoma model by inducing Th1-type immunity (37).…”

mentioning

confidence: 99%

In Vivo Antitumor Activity of NKT Cells Activated by the Combination of IL-12 and IL-18

Baxevanis

Gritzapis

Papamichail

2003

The Journal of Immunology

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Interleukin-12 and IL-18 have been demonstrated to potentiate innate immunity in a variety of experimental tumor models, but the functional roles of NK and/or NKT cells and their mechanism of action in these models have not been fully addressed. Through adoptive transfer of NKT cells activated in vitro with a combination of IL-12 plus IL-18 (IL-12/IL-18 NKT) into syngeneic animals, we demonstrate in this study that IL-12/IL-18 NKT cells are essential and collaborate with the host’s own NK cells in natural host immunity against the growth of ALC and MC57X syngeneic tumors. The relative roles of the adoptively transferred IL-12/IL-18 NKT cells and endogenous NK cells in host protection were first shown in normal C57BL/6 (B6) mice treated with anti-asialo GM1 Ab that selectively depletes NK cells; second, in B6.TCRJα281−/− mice specifically deficient for NKT cells; and third, in B6.scid mice that also lack NKT cells. Furthermore, by injecting normal B6 mice with anti-IL-2 and/or anti-IFN-γ mAb, we could demonstrate that effective innate immunity against both types of syngeneic tumors was dependent on the production of IL-2 and IFN-γ by the adoptively transferred NKT cells. In vitro studies confirmed both the secretion of IL-2 and IFN-γ by the IL-12/IL-18-activated NKT cells and their collaborative role with NK cells for lysis of ALC and MC57X syngeneic tumor targets. This is the first description of an antitumor function of IL-12/IL-18 NKT cells adoptively transferred into syngeneic hosts that provides the basis for a new modality in the cellular immunotherapy of cancer.

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Intratumoral IL-18 gene transfer improves therapeutic efficacy of antibody-targeted superantigen in established murine melanoma

Cited by 30 publications

References 44 publications

Adenovirus-mediated LIGHT gene modification in murine B-cell lymphoma elicits a potent antitumor effect

Adenovirus-mediated LIGHT gene modification in murine B-cell lymphoma elicits a potent antitumor effect

Oncolytic adenovirus expressing interleukin-18 induces significant antitumor effects against melanoma in mice through inhibition of angiogenesis

In Vivo Antitumor Activity of NKT Cells Activated by the Combination of IL-12 and IL-18

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