title: Zoledronic acid induces dose-dependent increase of antigen-specific CD8 T-cell responses in combination with peptide/poly-IC vaccine.
abstract: Zoledronic acid (ZA) is used for treating osteoporosis and for preventing skeletal fractures in cancer patients suffering from myeloma and prostate cancer. It is also reported to directly induce cancer cell apoptosis and indirectly modulate T-cell immune response as an antitumor agent. In this study, the effect of ZA following peptide/polyinosinic-polycytidylic acid (poly-IC) vaccination was investigated in a murine tumor model. The combination of ZA with peptide/poly-IC vaccine showed a synergistic effect on the induction of antigen-specific CD8 T-cell response. Three consecutive intravenous administrations of ZA was defined to induce the highest CD8 T-cell response. Further, total splenocyte counts and antigen-specific CD8 T-cell response gradually increased depending on the dose of ZA. In tumor-bearing mice, ZA showed a dose-dependent decrease of growth and prolonged survival. Treatment with ZA only decreased the number of CD11b(+)Gr1(+) myeloid cells in blood. Our results demonstrate that the use of ZA could improve antitumor immune responses induced by the peptide/poly-IC vaccine.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
authors.forename: Hye-Mi
authors.initials: HM
authors.lastname: Park
authors.affiliation: Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea; Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
authors.forename: Hyun-Il
authors.initials: HI
authors.lastname: Cho
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
authors.forename: Chang-Ae
authors.initials: CA
authors.lastname: Shin
authors.affiliation: Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Shon
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea; Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea; Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea. Electronic address: kimtg@catholic.ac.kr.
authors.forename: Tai-Gyu
authors.initials: TG
authors.lastname: Kim
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology*; D000077211:Zoledronic Acid
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004164:Diphosphonates; D007093:Imidazoles; D022223:Vaccines, Subunit; D000077211:Zoledronic Acid; D011070:Poly I-C
keywords: Anti-tumor effects; Antigen specific-CD8 T-cells; Peptide/poly-IC vaccine; Zoledronic acid (ZA)