Tumor suppression induced by intratumor administration of adenovirus vector expressing NK4, a 4-kringle antagonist of hepatocyte growth factor, and naive dendritic cells

Kikuchi, Toshiaki; Maemondo, Makoto; Narumi, Kunihiro; Matsumoto, Kunio; Nakamura, Toshikazu; Nukiwa, Toshihiro

doi:10.1182/blood-2002-04-1096

Cited by 41 publications

(47 citation statements)

References 34 publications

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“…E.G7-OVA cells were grown in complete RPMI 1640 containing 0.4 mg/ml G418 (Invitrogen, Carlsbad, CA). Dendritic cells were generated from mouse bone marrow precursors as described previously (21)(22)(23). LLC cells were maintained in complete DMEM (Sigma).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2004

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Section: Methodsmentioning

confidence: 99%

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

et al. 2004

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“…It has been reported that intratumoral injection of DCs induced antitumor effects. 33,34 In addition, HSP70-enhanced antigen uptake 19 and HSP70-induced DC maturation 20,21 have been reported. This indicates that injection of DCs directly into tumors releasing HSP70 after hyperthermia using magnetite nanoparticles is a possible approach for immune induction.…”

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confidence: 99%

Intratumoral injection of immature dendritic cells enhances antitumor effect of hyperthermia using magnetic nanoparticles

Tanaka

Ito

Kobayashi

et al. 2005

Intl Journal of Cancer

113

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Dendritic cells (DCs) are potent antigen-presenting cells that play a pivotal role in regulating immune responses in cancer and have recently been shown to be activated by heat shock proteins (HSPs). We previously reported that HSP70 expression after hyperthermia induces antitumor immunity. Our hyperthermia system using magnetite cationic liposomes (MCLs) induced necrotic cell death that was correlated with HSP70 release. In the present study, we investigated the therapeutic effects of DC therapy combined with MCL-induced hyperthermia on mouse melanoma. In an in vitro study, when immature DCs were pulsed with mouse B16 melanoma cells heated at 43°C, major histocompatibility complex (MHC) class I/II, costimulatory molecules CD80/ CD86 and CCR7 in the DCs were upregulated, thus resulting in DC maturation. C57BL/6 mice bearing a melanoma nodule were subjected to combination therapy using hyperthermia and DC immunotherapy in vivo by means of tumor-specific hyperthermia using MCLs and directly injected immature DCs. Mice were divided into 4 groups: group I (control), group II (hyperthermia), group III (DC therapy) and group IV (hyperthermia 1 DC therapy). Complete regression of tumors was observed in 60% of mice in group IV, while no tumor regression was seen among mice in the other groups. Increased cytotoxic T lymphocyte (CTL) and natural killer (NK) activity was observed on in vitro cytotoxicity assay using splenocytes in the cured mice treated with combination therapy, and the cured mice rejected a second challenge of B16 melanoma cells. This study has important implications for the application of MCL-induced hyperthermia plus DC therapy in patients with advanced malignancies as a novel cancer therapy. ' 2005 Wiley-Liss, Inc.Key words: hyperthermia; dendritic cell; antitumor immunity; magnetite cationic liposome; melanoma Hyperthermia has been used for many years to treat a wide variety of tumors in both experimental animals and patients. 1 The most commonly used heating method in clinical settings is capacitive heating using a radiofrequency (RF) electric field. 2 However, the problem with capacitive heating using an RF electric field is the difficulty in heating only the local tumor region at the intended temperature without damaging normal tissue, because electromagnetic energy is conducted from outside the body by penetrating normal tissue and is imperfectly transduced to heat; the heating characteristics are influenced by various factors, such as tumor size, position of electrodes, and adhesion of electrodes at uneven sites. Magnetic nanoparticles have thus been applied to hyperthermia in an attempt to overcome these disadvantages. 3,4 Magnetic nanoparticles act as a transducer to change electromagnetic energy to heat; such nanoparticles generate heat in an alternating magnetic field (AMF) due to hysteresis loss. As a result, only tissue accumulating magnetite nanoparticles is heated. 5 We subsequently developed magnetite cationic liposomes (MCLs) for use as an intracellular heating mediator. 6 MCLs were dev...

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“…IL-12 can promote the development of Th1 CD4 ϩ T cells, which facilitate maturation of CD8 ϩ CTLs whereas MIP-1␣ promotes CD8 ϩ T cell migration and their interaction with DCs. 37,38 Ad-mCD40L-activated A20 B cells are potent APCs as judged from the strong specific proliferative activity in an MLR. Infecting the cells with Ad-mIL-2, which resulted in mIL-2 production as a means to compensate for that normally produced during B7/CD28 interaction, had no effect on the surface phenotype of either MHC or costimulatory molecules.…”

Section: Discussionmentioning

confidence: 99%

Use of adenoviruses encoding CD40L or IL‐2 against B cell lymphoma

Meziane

Bhattacharyya

Armstrong

et al. 2004

Intl Journal of Cancer

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؉ T cell responses and cross reactive A20 Ig antibodies. Only vaccination with Ad-mCD40L-infected A20 cells produced a significant delay in tumor growth and long-term survival (p ‫؍‬ 0.0039). Stronger protective immunity to A20 challenge was generated by intravenous priming with A20 cells infected with Ad-mCD40L, Ad-mIL-2 or their combination followed by a boost immunization with A20 cells activated with syngeneic fibroblasts expressing CD40L. Compared to Ad-LacZ-infected A20 priming, the combination priming was most effective followed by Ad-mCD40L and Ad-mIL-2 (p ‫؍‬ 0.0027, p ‫؍‬ 0.0027, p ‫؍‬ 0.0163 respectively). Significant A20-specific CD8 ؉ T cell-mediated cytotoxicity was only demonstrated in splenocytes from these groups of vaccinated animals. By contrast, ELISPOT assay of splenocytes from all A20 prime/ boosted vaccinated groups demonstrated increases in ␥-interferon release by T cells elicited by in vitro stimulation either with A20 cells or another syngeneic 2PK-3 lymphoma, indicating the presence of cross reactive immunity. Similarly anti-A20 immunoglobulin antibodies generated after vaccination were not necessarily A20 idiotype-specific. Direct therapy of pre-established tumors was achieved with the combination of Ad-mCD40L and Ad-mIL-2 given at Days 4 and 8 at the tumor site with a significant long-term survival of 85% of tumor-bearing mice (p ‫؍‬ 0.0001). Our study strongly supports the use of Ad-CD40L and Ad-IL-2 combination therapy for the treatment of patients with B cell lymphoma.

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Tumor suppression induced by intratumor administration of adenovirus vector expressing NK4, a 4-kringle antagonist of hepatocyte growth factor, and naive dendritic cells

Cited by 41 publications

References 34 publications

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

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

Intratumoral injection of immature dendritic cells enhances antitumor effect of hyperthermia using magnetic nanoparticles

Use of adenoviruses encoding CD40L or IL‐2 against B cell lymphoma

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