title: Vγ9Vδ2 T cells and zoledronate mediate antitumor activity in an orthotopic mouse model of human chondrosarcoma.
abstract: Chondrosarcoma (CS) is a cartilaginous malignant neoplasm characterized by resistance to conventional adjuvant therapy. The prognosis of unresectable or metastatic CS is poor. Therefore, it is imperative to explore novel therapeutic approaches to improve the treatment efficacy for those CS patients. Emerging data has implicated the synergistic antitumor activity of zoledronate (ZOL) and Vγ9Vδ2 T cells. However, whether ZOL-stimulated Vγ9Vδ2 T cells could infiltrate bone sarcoma and inhibit tumor growth has not been thoroughly answered yet. In this study, Vγ9Vδ2 T cells from healthy donors and CS patients were expanded in the presence of ZOL (1 μM) and IL-2 (400 IU/ml). The antitumor activity of Vγ9Vδ2 T cells to ZOL-pretreated human CS was examined both in vitro and in vivo. ZOL pretreatment substantially enhanced the cytotoxicity of Vγ9Vδ2 T cells to SW1353 and primary CS cells. ZOL potentiated the migration and cytotoxicity of Vγ9Vδ2 T cells to SW1353 in dose- and time-dependent manner. Moreover, weekly intravenous ZOL followed by Vγ9Vδ2 T cells inhibited subcutaneous xenograft growth. Thus, Vγ9Vδ2 T cells were able to infiltrate bone tumor and significantly suppressed the development of orthotopic SW1353 xenografts. Altogether, the study raises the possibility of combining ZOL with Vγ9Vδ2 T cells for CS treatment.
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, Peoples Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Health Statistics, School of Medicine, Zhejiang University, Hangzhou, 310009, Peoples Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, Peoples Republic of China.|Department of Orthopaedics, The First People's Hospital of Wenling, Hangzhou, 310009, Peoples Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, Peoples Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, Peoples Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, Peoples Republic of China.
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, Peoples Republic of China. yezhaoming123@gmail.com.
authors.forename: Z
authors.initials: Z
authors.lastname: Ye
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D019264:Adoptive Transfer; D000328:Adult; D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002813:Chondrosarcoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays; D000077211:Zoledronic Acid
chemical_list: D000276:Adjuvants, Immunologic; D004164:Diphosphonates; D007093:Imidazoles; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid
keywords: Chondrosarcoma; Immunotherapy; Vγ9Vδ2 T cells; Zoledronate