PMID- 15825167 OWN - NLM STAT- MEDLINE DCOM- 20050824 LR - 20220318 IS - 0020-7136 (Print) IS - 0020-7136 (Linking) VI - 116 IP - 4 DP - 2005 Sep 10 TI - Intratumoral injection of immature dendritic cells enhances antitumor effect of hyperthermia using magnetic nanoparticles. PG - 624-33 AB - 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 degrees 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 + 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. CI - (c) 2005 Wiley-Liss, Inc. FAU - Tanaka, Kouji AU - Tanaka K AD - Department of Biotechnology, School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan. FAU - Ito, Akira AU - Ito A FAU - Kobayashi, Takeshi AU - Kobayashi T FAU - Kawamura, Tatsuyoshi AU - Kawamura T FAU - Shimada, Shinji AU - Shimada S FAU - Matsumoto, Kazuhiko AU - Matsumoto K FAU - Saida, Toshiaki AU - Saida T FAU - Honda, Hiroyuki AU - Honda H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (Cations) RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Liposomes) RN - 0 (Oxides) RN - E1UOL152H7 (Iron) RN - XM0M87F357 (Ferrosoferric Oxide) SB - IM MH - Animals MH - Cations MH - Dendritic Cells/*immunology MH - Electromagnetic Phenomena MH - Ferrosoferric Oxide MH - HSP70 Heat-Shock Proteins/biosynthesis MH - *Hyperthermia, Induced MH - Iron/*therapeutic use MH - Liposomes MH - Melanoma/*therapy/veterinary MH - Mice MH - *Nanostructures MH - Oxides/*therapeutic use MH - Skin Neoplasms/*therapy/veterinary MH - T-Lymphocytes, Cytotoxic EDAT- 2005/04/13 09:00 MHDA- 2005/08/25 09:00 CRDT- 2005/04/13 09:00 PHST- 2005/04/13 09:00 [pubmed] PHST- 2005/08/25 09:00 [medline] PHST- 2005/04/13 09:00 [entrez] AID - 10.1002/ijc.21061 [doi] PST - ppublish SO - Int J Cancer. 2005 Sep 10;116(4):624-33. doi: 10.1002/ijc.21061.