title: Antibody-dependent cellular cytotoxicity toward neuroblastoma enhanced by activated invariant natural killer T cells.
abstract: Anti-ganglioside GD2 antibodies mainly work through antibody-dependent cellular cytotoxicity (ADCC) and have demonstrated clinical benefit for children with neuroblastoma. However, high-risk neuroblastoma still has a high recurrence rate. For further improvement in patient outcomes, ways to maximize the cytotoxic effects of anti-GD2 therapies with minimal toxicity are required. Activated invariant natural killer T (iNKT) cells enhance both innate and type I acquired anti-tumor immunity by producing several kinds of cytokines. In this report, we investigated the feasibility of combination therapy using iNKT cells and an anti-GD2 antibody. Although some of the expanded iNKT cells expressed natural killer (NK) cell markers, including FcγR, iNKT cells were not directly associated with ADCC. When co-cultured with activated iNKT cells, granzyme A, granzyme B and interferon gamma (IFNγ) production from NK cells were upregulated, and the cytotoxicity of NK cells treated with anti-GD2 antibodies was increased. Not only cytokines produced by activated iNKT cells, but also NK-NKT cell contact or NK cell-dendritic cell contact contributed to the increase in NK cell cytotoxicity and further IFNγ production by iNKT cells and NK cells. In conclusion, iNKT cell-based immunotherapy could be an appropriate candidate for anti-GD2 antibody therapy for neuroblastoma.
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Mise
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Takami
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Kamata
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Harada
authors.affiliation: Department of Pediatric Surgery, Chiba Children's Hospital, Chiba, Japan.
authors.forename: Tomoro
authors.initials: T
authors.lastname: Hishiki
authors.affiliation: Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Terui
authors.affiliation: Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsunaga
authors.affiliation: Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Mitsuyuki
authors.initials: M
authors.lastname: Nakata
authors.affiliation: Center for Advanced Medicine, Chiba University Hospital, Chiba, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ikeuchi
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D055610:Antigens, CD1d / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology*; D009447:Neuroblastoma / Q000276:immunology / Q000628:therapy*
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; D016207:Cytokines
keywords: Antibody-dependent cellular cytotoxicity; immunotherapy; natural killer T cells; natural killer cells; neuroblastoma