Experimental Hematology
Volume 37, Issue 8 , Pages 956-968 , August 2009

Clinical and immunological evaluation of zoledronate-activated Vγ9γδ T-cell-based immunotherapy for patients with multiple myeloma

  • Yu Abe

      Affiliations

    • Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan
    • ,
  • Masato Muto

      Affiliations

    • Medinet Medical Institute, Tokyo, Japan
    • ,
  • Mie Nieda

      Affiliations

    • Medinet Medical Institute, Tokyo, Japan
    • Corresponding Author InformationOffprint requests to: Mie Nieda, Ph.D., Medinet Medical Institute, 2-2-8 Tamagawadai, Setagaya-ku, Tokyo 158-0096, Japan
    • ,
  • Yasunori Nakagawa

      Affiliations

    • Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan
    • ,
  • Andrew Nicol

      Affiliations

    • Centre for Immune and Targeted Therapy, University of Queensland, Greenslopes Private Hospital, Brisbane, Australia
    • ,
  • Touru Kaneko

      Affiliations

    • Seta Clinic Group, Tokyo, Japan
    • ,
  • Shigenori Goto

      Affiliations

    • Seta Clinic Group, Tokyo, Japan
    • ,
  • Kiyoshi Yokokawa

      Affiliations

    • Medinet Co. Ltd, Tokyo, Japan
    • ,
  • Kenshi Suzuki

      Affiliations

    • Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan

Received 18 September 2008 ,Revised 23 April 2009 ,Accepted 23 April 2009.

References 

  1. Attal M, Harousseau JL, Atoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med. 1996;335:91–97
  2. Smyth MJ, Godfrey DI, Trapani JA. A fresh look at tumor immunosurveillance and immunotherapy. Nat Immunol. 2001;2:293–299
  3. Kelly JM, Darcy PK, Markby JL, et al. Induction of tumor-specific T cell memory by NK cell-mediated tumor rejection. Nat Immunol. 2002;3:83–90
  4. Ferrarini M, Ferrero E, Dagna L, Poggi A, Zocchi MR. Human γδ T cells: a nonredundant system in the immune-surveillance against cancer. Trends Immunol. 2002;23:14–18
  5. Kabeliz D, Wesch D, Pitters E, Zöller M. Potential of human γδ T lymphocytes for immunotherapy of cancer. Int J Cancer. 2004;112:727–732
  6. Lopez RD. Human γδ-T cells in adoptive immunotherapy of malignant and infectious disease. Immunol Res. 2002;26:207–221
  7. Mariani S, Muraro M, Pantaleoni L, et al. Effector γδ T cells and tumor cells as immune targets of zoledronic acid in multiple myeloma. Leukemia. 2005;19:664–670
  8. Kabeliz D, Wesch D, Pitters E, Zoller M. Potential of human gammadelta T lymphocytes for immunotherapy of cancer. Int J Cancer. 2004;112:727–732
  9. Tanaka Y, Morita CT, Tanaka Y, Nieves E, Brenner MB, Bloom BR. Natural and synthetic non-peptide antigens recognized by human γδ T cells. Nature. 1995;375:155–158
  10. Bukowski JF, Morita CT, Brenner MB. Human γδ T cells recognize alkylamines derived from microbes, edible plants, and tea: implications for innate immunity. Immunity. 1999;11:57–65
  11. Kunzmann V, Bauer E, Wilhelm M. γ/δ T-cell stimulation by pamidronate. N Engl J Med. 1999;340:737–738
  12. Kunzmann V, Bauer E, Feurle J, Weissinger F, Tony HP, Wilhelm M. Stimulation of γδ T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood. 2000;96:384–392
  13. Dieli F, Vermijlen D, Fulfaro F, et al. Targeting human γδ T cells with zoledronate and interleukin-2 for immunotherapy of hormone-refractory prostate cancer. Cancer Res. 2007;67:7450–7457
  14. Märten A, Lilienfeld-Toal M, Büchler MW, Schmidt J. Zoledronic acid has direct antiproliferative and antimetastatic effect on pancreatic carcinoma cells and acts as an antigen for δ2 γ/δ T cells. J Immunother. 2007;30:370–377
  15. Mattarollo SR, Kenna T, Nieda M, Nicol AJ. Chemotherapy and zoledronate sensitize solid tumor cells to Vγ9Vδ2 T cell cytotoxicity. Cancer Immunol Immunother. 2007;56:1285–1297
  16. Davodeau F, Peyrat MA, Hallet MM, et al. Close correlation between Daudi and mycobacterial antigen recognition by human gamma delta T cells and expression of V9JPC1 gamma/V2DJC delta-encoded T cell receptors. J Immunol. 1993;151:1214–1223
  17. Selin LK, Stewart S, Shen C, Mao HQ, Wilkins JA. Reactivity of gamma delta T cells induced by the tumor cell line RPMI 8226: functional heterogeneity of clonal population and role of GroEL heat shock proteins. Scand J Immunol. 1992;36:107–117
  18. Tokuyama H, Hagi T, Mattarollo SR, et al. Vγ9Vδ2 T cell cytotoxicity against tumor cells is enhanced by monoclonal antibody drugs-Rituximab and trastuzumab. Int J Cancer. 2008;112:2526–2534
  19. Wilhelm M, Kunzmann V, Eckstein S, et al. γδ T cells for immune therapy of patients with lymphoid malignancies. Blood. 2003;102:200–206
  20. Kobayashi H, Tanaka Y, Yagi J, et al. Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study. Cancer Immunol Immunother. 2007;56:469–476
  21. Caccamo N, Meraviglia S, Ferlazzo V, et al. Differential requirements for antigen or homeostatic cytokines for proliferation and differentiation of human Vγ9Vδ2 naïve, memory and effector T cell subsets. Eur J Immunol. 2005;35:1764–1772
  22. Gioia C, Agrati C, Casetti R, et al. Lack of CD27-CD45RA-Vγ9Vδ2+ T cell effectors in immunocompromised hosts and during active pulmonary tuberculosis. J Immunol. 2002;168:1484–1489
  23. Kondo M, Sakuta K, Noguchi A, et al. Zoledronate facilitates large-scale ex vivo expansion of functional δ2 T cells from cancer patients for use in adaptive immunotherapy. Cytotherapy. 2008;136:159–167
  24. Sasawatari S, Tadaki T, Isogai M, et al. Efficient priming and expansion of antigen-specific CD8+ T cells by a novel cell-based artificial APC. Immunol Cell Biol. 2006;84:512–521
  25. Bauer S, Groh V, Wu J, et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 1999;285:727–729
  26. Das H, Groh V, Kuijl C, et al. MICA engagement by human Vγ9Vδ2 T cells enhances their antigen-dependent effector function. Immunity. 2001;15:83–93
  27. Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein KH, Spies T. Broad tumor-associated expression and recognition by tumor-derived γδ T cells of MICA and MICB. Proc Natl Acad Sci U S A. 1996;96:6879–6884
  28. Kryczek I, Wei S, Zou L, et al. Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment. J Immunol. 2007;178:6730–6733
  29. Dieli F, Gebbia N, Poccia F, et al. Induction of γδ T-lymphocyte effector functions by bisphosphonate zoledronic acid in cancer patients in vivo. Blood. 2003;102:2310–2311
  30. Jinushi M, Takehara T, Tatsumi T, et al. Impairment of natural killer cell and dendritic cell functions by the soluble form of MHC class I-related chain A in advanced human hepatocellular carcinomas. J Hepatol. 2005;43:1013–1020
  31. Kato Y, Tanaka Y, Hayashi M, Okawa K, Minato N. Involvement of CD166 in the activation of human γδ T cells by tumor cells sensitized with nonpeptide antigens. J Immunol. 2006;177:877–884
  32. Moser B, Brandes M. γδ T cells: an alternative type of professional APC. Trends Immunol. 2006;27:112–118
  33. Girlanda S, Fortis C, Belloni D, et al. MICA expressed by multiple myeloma and monoclonal gammopathy of undetermined significance plasma cells costimulates pamidronate-activated gammadelta lymphocytes. Cancer Res. 2005;65:7502–7508
  34. Carbone E, Neri P, Mesuraca M, et al. HLA class I, NKG2D and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells. Blood. 2005;105:251–258
  35. Groh V, Wu J, Yee C, Spies T. Tumor-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature. 2002;419:734–738

 Drs. Abe and Muto contributed equally to this work.

PII: S0301-472X(09)00138-6

doi: 10.1016/j.exphem.2009.04.008

Experimental Hematology
Volume 37, Issue 8 , Pages 956-968 , August 2009

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