Adoptive transfer of ex vivo expanded Vγ9Vδ2 T cells in combination with zoledronic acid inhibits cancer growth and limits osteolysis in a murine model of osteolytic breast cancer

被引:20
作者
Zysk, Aneta [1 ]
DeNichilo, Mark O. [1 ]
Panagopoulos, Vasilios [1 ]
Zinonos, Irene [1 ]
Liapis, Vasilios [1 ]
Hay, Shelley [1 ]
Ingman, Wendy [2 ]
Ponomarev, Vladimir [3 ]
Atkins, Gerald [4 ]
Findlay, David [4 ]
Zannettino, Andrew [5 ]
Evdokiou, Andreas [1 ]
机构
[1] Univ Adelaide, Basil Hetzel Inst, Breast Canc Res Unit, Discipline Surg, Adelaide, SA, Australia
[2] Univ Adelaide, Basil Hetzel Inst, Breast Canc Res Unit, Discipline Surg, Adelaide, SA, Australia
[3] Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA
[4] Univ Adelaide, Discipline Orthopaed & Trauma, Adelaide, SA, Australia
[5] Univ Adelaide, Sch Med Sci, Myeloma Res Lab Canc Theme, South Australian Hlth & Med Res Inst,Fac Hlth Sci, Adelaide, SA 5005, Australia
关键词
Metastasis; Immunotherapy; Bisphosphonate; Osteoclast; Tumour associated macrophage; GAMMA-DELTA; 3RD-GENERATION BISPHOSPHONATE; PERIPHERAL-BLOOD; IN-VITRO; ANTITUMOR-ACTIVITY; ANTICANCER AGENTS; BONE; METASTASIS; IMMUNOTHERAPY; PROLIFERATION;
D O I
10.1016/j.canlet.2016.11.013
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Bone metastases occur in over 75% of patients with advanced breast cancer and are responsible for high levels of morbidity and mortality. In this study, ex vivo expanded cytotoxic V gamma 9V delta 2 T cells isolated from human peripheral blood were tested for their anti-cancer efficacy in combination with zoledronic acid (ZOL), using a mouse model of osteolytic breast cancer. In vitro, expanded V gamma 9V delta 2 T cells were cytotoxic against a panel of human breast cancer cell lines, and ZOL pre-treatment further sensitised breast cancer cells to killing by V gamma 9V delta 2 T cells. V gamma 9V delta 2. T cells adoptively transferred into NOD/SCID mice localised to osteolytic breast cancer lesions in the bone, and multiple infusions of V gamma 9V delta 2 T cells reduced tumour growth in the bone. ZOL pre-treatment potentiated the anti-cancer efficacy of V gamma 9V delta 2 T cells, with mice showing further reductions in tumour burden. Mice treated with the combination also had reduced tumour burden of secondary pulmonary metastases, and decreased bone degradation. Our data suggests that adoptive transfer of V gamma 9V delta 2 T cell in combination with ZOL may prove an effective immunotherapeutic approach for the treatment of breast cancer bone metastases. (C) 2016 Published by Elsevier Ireland Ltd.
引用
收藏
页码:141 / 150
页数:10
相关论文
共 54 条
  • [1] Human V2V2 T cells limit breast cancer growth by modulating cell survival-, apoptosis-related molecules and microenvironment in tumors
    Aggarwal, Reeva
    Lu, Jingwei
    Kanji, Suman
    Das, Manjusri
    Joseph, Matthew
    Lustberg, Maryam B.
    Ray, Alo
    Pompili, Vincent J.
    Shapiro, Charles L.
    Das, Hiranmoy
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2013, 133 (09) : 2133 - 2144
  • [2] Adoptively transferred ex vivo expanded γδ-T cells mediate in vivo antitumor activity in preclinical mouse models of breast cancer
    Beck, Benjamin H.
    Kim, Hyung-Gyoon
    Kim, Hyunki
    Samuel, Sharon
    Liu, Zhiyong
    Shrestha, Robin
    Haines, Hilary
    Zinn, Kurt
    Lopez, Richard D.
    [J]. BREAST CANCER RESEARCH AND TREATMENT, 2010, 122 (01) : 135 - 144
  • [3] High Phosphoantigen Levels in Bisphosphonate-Treated Human Breast Tumors Promote Vγ9Vδ2 T-Cell Chemotaxis and Cytotoxicity In Vivo
    Benzaid, Ismahene
    Moenkkoenen, Hannu
    Stresing, Verena
    Bonnelye, Edith
    Green, Jonathan
    Moenkkoenen, Jukka
    Touraine, Jean-Louis
    Clezardin, Philippe
    [J]. CANCER RESEARCH, 2011, 71 (13) : 4562 - 4572
  • [4] Boissier S, 2000, CANCER RES, V60, P2949
  • [5] γδ T cells:: Functional plasticity and heterogeneity
    Carding, SR
    Egan, PJ
    [J]. NATURE REVIEWS IMMUNOLOGY, 2002, 2 (05) : 336 - 345
  • [6] THE CLINICAL COURSE OF BONE METASTASES FROM BREAST-CANCER
    COLEMAN, RE
    RUBENS, RD
    [J]. BRITISH JOURNAL OF CANCER, 1987, 55 (01) : 61 - 66
  • [7] Metastatic bone disease: clinical features, pathophysiology and treatment strategies
    Coleman, RE
    [J]. CANCER TREATMENT REVIEWS, 2001, 27 (03) : 165 - 176
  • [8] Visualizing mineral binding and uptake of bisphosphonate by osteoclasts and non-resorbing cells
    Coxon, Fraser P.
    Thompson, Keith
    Roelofs, Anke J.
    Ebetino, F. Hal
    Rogers, Michael J.
    [J]. BONE, 2008, 42 (05) : 848 - 860
  • [9] Targeting myeloma-osteoclast interaction with Vγ9Vδ2 T cells
    Cui, Qu
    Shibata, Hironobu
    Oda, Asuka
    Amou, Hiroe
    Nakano, Ayako
    Yata, Kenichiro
    Hiasa, Masahiro
    Watanabe, Keiichiro
    Nakamura, Shingen
    Miki, Hirokazu
    Harada, Takeshi
    Fujii, Shiro
    Kagawa, Kumiko
    Takeuchi, Kyoko
    Ozaki, Shuji
    Matsumoto, Toshio
    Abe, Masahiro
    [J]. INTERNATIONAL JOURNAL OF HEMATOLOGY, 2011, 94 (01) : 63 - 70
  • [10] Vγ9Vγ2 T Lymphocytes Efficiently Recognize and Kill Zoledronate-Sensitized, Imatinib-Sensitive, and Imatinib-Resistant Chronic Myelogenous Leukemia Cells
    D'Asaro, Matilde
    La Mendola, Carmela
    Di Liberto, Diana
    Orlando, Valentina
    Todaro, Matilde
    Spina, Marisa
    Guggino, Giuliana
    Meraviglia, Serena
    Caccamo, Nadia
    Messina, Angelo
    Salerno, Alfredo
    Di Raimondo, Francesco
    Vigneri, Paolo
    Stassi, Giorgio
    Fournie, Jean Jacques
    Dieli, Francesco
    [J]. JOURNAL OF IMMUNOLOGY, 2010, 184 (06) : 3260 - 3268