Antitumor Immunity by Magnetic Nanoparticle-Mediated Hyperthermia

Table 1.  Representative magnetic nanoparticles for magnetic nanoparticle-mediated hyperthermia.

Name	Core size	Characteristics	Ref.
Magnetite	A few μm	The first demonstration using magnetic particles	[15]
Dextran magnetite	6 nm	The first demonstration using magnetite of nanometer sizes	[16]
Aminosilane-coated magnetite	15 nm	Enhances the uptake by cancer cells and prevents intracellular digestion	[5]
Magnetite cationic liposome or cationic protein	10 nm	Enhances the uptake by cancer cells and stabilizes the colloidal solution	[17–18,20]
NPrCAP-conjugated magnetic nanoparticle	10 nm	Targets melanoma cells and exerts chemotherapeutic effects	[21–23]
Antibody-conjugated magnetic nanoparticle	20 nm	Targets human breast cancer and is conjugated with radioactive indium	[24]
Antibody or aptamer-conjugated magnetic nanoparticle	10 nm	Targets tumor cells and stabilizes the colloidal solution	[25–28]
Magnetic nanoparticle with encapsulated antitumor drug	20–30 nm	Controlled drug release	[29,30]

NPrCAP: N-propionyl-cysteaminylphenol.

Table 2.  Summary of a Phase I clinical trial at Nagoya University Hospital, Japan.

Cancer type	Age (years)/sex	Site	Pathological effect	Adverse effects
Papillary thyroid	79/female	Anterior neck	1a	None
Breast	52/female	Right side chest	2	None
Papillary thyroid	45/female	Left neck	0	None
Tongue	34/male	Left neck	0	None
Soft-tissue sarcoma	32/female	Right sole Right knee occipital	1b 1a	None
Follicular thyroid	55/male	Right neck (center of the target) Right neck (pheripheal zone of the target)	3 1a	None

Pathological effect: 0 = ineffective; 1a = minor effect; 1b = moderate effect; 2 = considerable effect; 3 = complete effect.

Authors and Disclosures

Takeshi Kobayashi*^,1, Kazuhiro Kakimi², Eiichi Nakayama³ & Kowichi Jimbow^4,5

¹Research Institute for Biological Functions, Chubu University, Matsumoto-cho 1200, Kasugai, Aichi 487-8501, Japan
²Department of Immunotherapeutics (Medinet), University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-8655, Japan
³Faculty of Health & Welfare, Kawasaki University of Medical Welfare, 288 Matsushima, Kurashiki, Okayama 701-0193, Japan
⁴Institute of Dermatology & Cutaneous Sciences, Sapporo 060-0042, Japan
⁵Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan

*Author for correspondence
Tel.: +81 568 51 6342 Fax: +81 568 52 6594 kobatake@isc.chubu.ac.jp

Sidebar

Executive Summary

Magnetic nanoparticles suitable for magnetic nanoparticle-mediated hyperthermia

• Magnetic nanoparticle-mediated hyperthermia (MNHT) consists of two major, stepwise technical approaches: the first is to accumulate magnetic nanoparticles (MNPs) into the tumor tissue, and the second is to apply an alternating magnetic field in order to generate local heat through nanoparticles within the tumor tissue.

• Almost all of the MNPs developed in the past are injected directly into tumor tissues. However, several forms of MNPs with tumor-specific tags have been given via systemic administration and found to bind selectively to tumor tissues.

Processes of immunogenic cell death by MNHT & hyperthermia-induced heat-shock proteins

• In vivo experimental studies have indicated that MNHT can induce the regression of not only local tumor tissue exposed to heat, but also distant metastatic tumors unexposed to heat.

• Immunogenic cell death induced by hyperthermia contributes to therapeutic outcomes in terms of a long-term antitumor effect rather than a short-term, direct cytotoxic effect on tumor cells.

• MNHT enhances the expression of HSP70, which chaperons tumor antigens and increases immunogenicity during hyperthermia treatment.

Mechanism of antitumor immunity induced by MNHT

• The antitumor activity of MNHT may consist of two major arms: a direct killing effect by hyperthermia and an indirect, immune-mediated antitumor effect.

• The antitumor immune response induced by MNHT derives from the release of heat-shock protein–peptide complexes from the degraded tumor cells.

Combined effects of MNHT-induced hyperthermia & immunotherapy & future clinical trials

• Several preliminary clinical trials have been recently conducted based upon many in vivo animal experiments. However, further efforts should be directed towards optimizing the combined effects of direct heat-mediated cell death and indirect immune-mediated cell death in order to develop a better antitumor approach with MNHT.