title: Combination therapy with dendritic cell vaccine and IL-2 encapsulating polymeric micelles enhances intra-tumoral accumulation of antigen-specific CTLs.
abstract: Dendritic cell (DC) vaccine is a promising immunotherapy for cancer due to its ability to induce antigen-specific CTLs efficiently. However, a number of clinical studies have implied insufficient therapeutic benefits with the use of MHC class 1 restricted peptide-pulsed DC vaccine. To enhance the clinical efficacy, we examined combination therapy of DC vaccine pulsed with OVA peptide and intravenous low dose unmodified IL-2 (IL-2 solution) administration against EG7 tumor-bearing mice. Unexpectedly, no additional effects of IL-2 solution were observed on CTL induction and the therapeutic effects of DC vaccine, possibly because of the short half-life of IL-2 in plasma. Therefore, we generated IL-2-encapsulating polymeric micelles (IL-2 micelle), which showed prolonged IL-2 retention in the circulation after intravenous administration compared with IL-2 solution. When mice were treated with OVA peptide-pulsed DCs in combination with IL-2 micelle, OVA-specific CTLs were efficiently induced in the spleen in comparison with DC vaccine combined with IL-2 solution or DC vaccine alone. In addition, combination therapy of DC vaccine and IL-2 micelle against EG7 tumor-bearing mice induced the efficient accumulation of antigen-specific CTLs into the tumor and marked anti-tumor effects. Thus, the administration of IL-2 micelle can significantly enhance DC vaccine efficacy against tumors.
authors.affiliation: Medinet Medical Institute, MEDINET Co., Ltd., Setagaya, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Miki
authors.affiliation: Medinet Medical Institute, MEDINET Co., Ltd., Setagaya, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nagaoka
authors.affiliation: Research Division, NanoCarrier Co., Ltd., Kashiwa, Chiba, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Harada
authors.affiliation: Research Division, NanoCarrier Co., Ltd., Kashiwa, Chiba, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Medinet Medical Institute, MEDINET Co., Ltd., Setagaya, Tokyo, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Jinguji
authors.affiliation: Research Division, NanoCarrier Co., Ltd., Kashiwa, Chiba, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Medinet Medical Institute, MEDINET Co., Ltd., Setagaya, Tokyo, Japan. Electronic address: maekawa@medinet-inc.co.jp.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Maekawa
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism*; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004359:Drug Therapy, Combination; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D009374:Neoplasms, Experimental / Q000628:therapy*; D010047:Ovalbumin / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments; D011108:Polymers; D051381:Rats; D017208:Rats, Wistar; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
chemical_list: D000941:Antigens; D019496:Cancer Vaccines; D007376:Interleukin-2; D008823:Micelles; D010446:Peptide Fragments; D011108:Polymers; D010047:Ovalbumin
keywords: Cytotoxic T lymphocytes; Dendritic cells; Drug delivery system; Immunotherapy; Interleukin-2