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Review
. 2006 Mar;55(3):320-8.
doi: 10.1007/s00262-005-0049-y. Epub 2005 Aug 25.

Cancer immunotherapy based on intracellular hyperthermia using magnetite nanoparticles: a novel concept of "heat-controlled necrosis" with heat shock protein expression

Akira Ito  1 , Hiroyuki Honda, Takeshi Kobayashi
Affiliations
Review

Cancer immunotherapy based on intracellular hyperthermia using magnetite nanoparticles: a novel concept of "heat-controlled necrosis" with heat shock protein expression

Akira Ito et al. Cancer Immunol Immunother. 2006 Mar.

Abstract

Heat shock proteins (HSPs) are highly conserved proteins whose syntheses are induced by a variety of stresses, including heat stress. Since the expression of HSPs, including HSP70, protects cells from heat-induced apoptosis, HSP expression has been considered to be a complicating factor in hyperthermia. On the other hand, recent reports have shown the importance of HSPs, such as HSP70, HSP90 and glucose-regulated protein 96 (gp96), in immune reactions. If HSP expression induced by hyperthermia is involved in tumor immunity, novel cancer immunotherapy based on this novel concept can be developed. In such a strategy, a tumor-specific hyperthermia system, which can heat the local tumor region to the intended temperature without damaging normal tissue, would be highly advantageous. To achieve tumor-specific hyperthermia, we have developed an intracellular hyperthermia system using magnetite nanoparticles. This novel hyperthermia system can induce necrotic cell death via HSP expression, which induces antitumor immunity. In the present article, cancer immunology and immunotherapy based on hyperthermia, and HSP expression are reviewed and discussed.

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Figures

Fig. 1
Fig. 1
Hyperthermia using magnetite nanoparticles. a Scheme of hyperthermia treatment. Magnetite nanoparticles are concentrated in tumor tissue by the DDS. Then the nanoparticles are irradiated with an AMF produced outside the human body, resulting in tumor-specific hyperthermia. b Liposomal drugs containing magnetite nanoparticles for DDS. Left antibody-conjugated magnetoliposome (AML); right magnetite cationic liposome (MCL)
Fig. 2
Fig. 2
Anticancer immune response induced by hyperthermia using magnetite nanoparticles. Rats bearing tumors on each side of the body were prepared. MCLs were injected into the left tumor only, and the rats were irradiated with an AMF using the apparatus shown in (a, left). Temperature of left tumor, containing MCLs (closed circles), increased specifically, whereas temperature of right tumor (open circles) and rectum (open triangles) remained below 38°C (a, right). The tumor-specific hyperthermia treatment induced an antitumor immune response, and both tumors had disappeared on the 28th day after hyperthermia treatment. I Control rat without AMF irradiation; II rat with AMF irradiation. Open triangles in (b), the side without MCLs; closed triangle in (b), the side with MCLs
Fig. 3
Fig. 3
Relay line model for tumor antigenic peptide transfer during antigen processing and presentation by HSPs. HSP family, including HSP70 and HSP90 in cytoplasm, and gp96 in ER, is involved in peptide transfer to MHC class I molecule
Fig. 4
Fig. 4
Mechanism of induction of anticancer immune response by hyperthermia. Augmentation of tumor immunogenicity by an increase of the number of MHC molecules on the surface of cancer cells via inducible HSP expression
Fig. 5
Fig. 5
Mechanism of induction of anticancer immune response by hyperthermia. In-situ vaccination by HSP-peptide complexes released from dying cells via necrosis by hyperthermia treatment
Fig. 6
Fig. 6
Proposed scenario of the mechanism of induction of anticancer immune response by hyperthermia
See this image and copyright information in PMC

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