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Antitumor effects of combined therapy of recombinant heat shock protein 70 and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma

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Abstract

Heat shock proteins (HSPs) are recognized as significant participants in cancer immunity. We previously reported that HSP70 expression following hyperthermia using magnetic nanoparticles induces antitumor immunity. In the present study, we examine whether the antitumor immunity induced by hyperthermia is enhanced by administration of recombinant HSP70 protein into the tumor in situ. Hyperthermia was conducted using our original magnetite cationic liposomes (MCLs), which have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis loss. MCLs and recombinant mouse HSP70 (rmHSP70) were injected into melanoma nodules in C57BL/6 mice, which were subjected to AMF for 30 min. Temperature within the tumor reached 43°C and was maintained by controlling the magnetic field intensity. The combined treatment strongly inhibited tumor growth over a 30-day period and complete regression of tumors was observed in 20% (2/10) of mice. It was also found that systemic antitumor immunity was induced in the cured mice. This study suggests that novel combined therapy using exogenous HSP70 and hyperthermia has great potential in cancer treatment.

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Acknowledgements

The authors would like to thank Toda Kogyo Co. for supplying the magnetite. This work was partially supported by a Grant-in-Aid for Scientific Research (No. 13853005 and 15760587), the University Start-Up Creation Support System and the 21st Century COE Program “Nature-Guided Materials Processing” from the Ministry of Education, Science, Sports and Culture of Japan.

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Correspondence to Takeshi Kobayashi.

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Ito, A., Matsuoka, F., Honda, H. et al. Antitumor effects of combined therapy of recombinant heat shock protein 70 and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma. Cancer Immunol Immunother 53, 26–32 (2004). https://doi.org/10.1007/s00262-003-0416-5

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  • DOI: https://doi.org/10.1007/s00262-003-0416-5

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