Heat shock protein 70 gene therapy combined with hyperthermia using magnetic nanoparticles

Ito, Akira; Matsuoka, Fumiko; Honda, Hiroyuki; Kobayashi, Takeshi

doi:10.1038/sj.cgt.7700648

Cited by 86 publications

(44 citation statements)

References 41 publications

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“…However, traditional heating temperature had achieved non-ideal therapeutic effect; in fact, some researchers had reported that traditional methods promoted the growth of tumor cells (25)(26)(27)(28). Nevertheless, in the present study, we have found a novel and potentially useful technique in applying magnetic fluid hyperthermia (MFH) on mouse pancreatic cancer models using a unique mouse pancreatic cancer cell line (MPC-83), established by us in 1983.…”

Section: Introductionmentioning

confidence: 83%

Anticancer effect and feasibility study of hyperthermia treatment of pancreatic cancer using magnetic nanoparticles

Dong

2011

Oncol Rep

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Abstract.We investigated the effect and feasibility of hyperthermia treatment on subcutaneous pancreatic cancer in female Kunming mice, using a murine pancreatic cancer cell line (MPC-83) established by us and found in this study to originate from epithelial pancreatic acinus. Magnetic fluid (MF) with ferromagnetic particles of about 20 nm in size was used as a heating mediator. MF was injected into the subcutaneous nodules with subaxillary regions of mice 10 days after tumor transplantation; homogeneous distribution of magnetic nanoparticles in nodules was easily detected by X-ray 24 h later. Mice were allocated to four groups as follows: no treatment (control); MF injection alone; alternating magnetic field (AMF) irradiation alone; and MF injection and hyperthermia generated by applying AMF (300 kHz, 110 Gs). The two hyperthermia-treated subgroup tumors reached central temperatures of 47 and 51˚C, respectively, for 30 min; while rectal temperature in both subgroups remained below 36˚C. Tumor growth was inhibited and survival significantly prolonged in the hyperthermia group compared with other groups (P<0.05). Tumor cells near the MF in the hyperthermia group apoptosed or necrosed immediately after hyperthermia. By day 14, there were no subcutaneous nodules; and residual magnetic nanoparticles were ingested by phagocytes. Nuclear proliferating cell nuclear antigen (PCNA) decreased in hyperthermia group tumor cells compared to the other groups; cytoplasmic heat shock protein 70 (HSP 70) was conspicuously higher immediately after hyperthermia (P<0.05). This technique had therapeutic potential and provided a new idea in the treatment of pancreatic cancer.

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Section: Introductionmentioning

confidence: 83%

Anticancer effect and feasibility study of hyperthermia treatment of pancreatic cancer using magnetic nanoparticles

Dong

2011

Oncol Rep

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“…An acute excess achieved by repeated Hsp70 gene transfer alone or in combination with hyperthermia proved to kill large established melanoma or to arrest tumor growth in mice, respectively [44,58]. Alternatively, an acute excess of Hsp70 induced by different therapies of human melanomas [1,43] may be utilized to stimulate the immune system against resistant tumor populations.…”

Section: Discussionmentioning

confidence: 99%

Lysosomal Rerouting of Hsp70 Trafficking as a Potential Immune Activating Tool for Targeting Melanoma

Juhász¹,

Thuenauer²,

Spachinger³

et al. 2012

CPD

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Tumor specific cell surface localization and release of the stress inducible heat shock protein 70 (Hsp70) stimulate the immune system against cancer cells. A key immune stimulatory function of tumor-derived Hsp70 has been exemplified with the murine melanoma cell model, B16 overexpressing exogenous Hsp70. Despite the therapeutic potential mechanism of Hsp70 transport to the surface and release remained poorly understood. We investigated principles of Hsp70 trafficking in B16 melanoma cells with low and high level of Hsp70. In cells with low level of Hsp70 apparent trafficking of Hsp70 was mediated by endosomes. Excess Hsp70 triggered a series of changes such as a switch of Hsp70 trafficking from endosomes to lysosomes and a concomitant accumulation of Hsp70 in lysosomes. Moreover, lysosomal rerouting resulted in an elevated concentration of surface Hsp70 and enabled active release of Hsp70. In fact, hyperthermia, a clinically applicable approach triggered immediate active lysosomal release of soluble Hsp70 from cells with excess Hsp70. Furthermore, excess Hsp70 enabled targeting of internalized surface Hsp70 to lysosomes, allowing in turn heat-induced secretion of surface Hsp70. Altogether, we show that excess Hsp70 expressed in B16 melanoma cells diverts Hsp70 trafficking from endosomes to lysosomes, thereby supporting its surface localization and lysosomal release. Controlled excess-induced lysosomal rerouting and secretion of Hsp70 is proposed as a promising tool to stimulate anti-tumor immunity targeting melanoma.

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“…Since HSPs function as natural and powerful immunostimulants, recombinant HSP70 therapy 64) or HSP70 gene therapy 65) could be a possible approach. For recombinant HSP70 therapy, MCLs and recombinant mouse HSP70 were injected into melanoma nodules in C57BL/6 mice, which were subjected to hyperthermia at 43°C for 30 min.…”

Section: Development Of Novel Cancer Immunotherapy Based On Heat-indumentioning

confidence: 99%

Heat immunotherapy with heat shock protein expression by hyperthermia using magnetite nanoparticles

Ito

Kobayashi

Honda

2007

Ann. Cancer Res. Therap.

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Abbreviations: heat shock protein, HSP; drug delivery system, DDS; magnetite cationic liposome, MCLs; antibody-conjugated magnetoliposome, AML; monoclonal antibody, MAb; natural killer, NK; metallothionein-I, MT; glucose-regulated protein 96, gp96; major histocompatibility complex, MHC; endoplasmic reticulum, ER; transporter associated with antigen processing, TAP; cytotoxic T lymphocyte, CTL; antigenpresenting cell, APC; dendritic cell, DC; nuclear factor, NF; tumor necrosis factor, TNF; interleukin, IL; macrophage inflammatory protein, MIP; macrophage chemotactic protein, MCP; regulated upon activation normal T cell expressed and secreted, RANTES; nitric oxide, NO; granulocyte macrophage-colony stimulating factor, GM-CSF; interferon, IFN. AbstractHyperthermia is a possible approach for cancer therapy. However, a major technical problem associated with the use of hyperthermia is the difficulty of heating the local tumor region to the intended temperature without damaging normal tissue. Accordingly, in hyperthermia treatment, the expression of heat shock proteins (HSPs) has been considered a complicating factor because the expression of HSPs protects cells from apoptotic cell death. In cancer immunity, on the other hand, HSPs, including HSP70, have been shown to play an important role in immune reactions. If HSP expression induced by hyperthermia is involved in tumor immunity, novel cancer immunotherapy based on hyperthermia treatment can be developed. In such a strategy, a tumor-specific hyperthermia system that can induce necrotic cell death via HSP expression without damaging non-cancerous tissues would be highly advantageous. An intracellular hyperthermia system using functionalized magnetite nanoparticles, including magnetite cationic liposomes and antibody-conjugated magnetoliposomes, facilitates tumor-specific hyperthermia; this can induce necrotic cell death via HSP expression, which in turn induces antitumor immunity. We term this novel cancer therapy as "heat immunotherapy." This review discusses recent progress in cancer immunology via HSP expression and novel immunotherapy based on hyperthermia.

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Heat shock protein 70 gene therapy combined with hyperthermia using magnetic nanoparticles

Cited by 86 publications

References 41 publications

Anticancer effect and feasibility study of hyperthermia treatment of pancreatic cancer using magnetic nanoparticles

Anticancer effect and feasibility study of hyperthermia treatment of pancreatic cancer using magnetic nanoparticles

Lysosomal Rerouting of Hsp70 Trafficking as a Potential Immune Activating Tool for Targeting Melanoma

Heat immunotherapy with heat shock protein expression by hyperthermia using magnetite nanoparticles

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