Phase I/II study of adoptive transfer of γδ T cells in combination with zoledronic acid and IL-2 to patients with advanced renal cell carcinoma

Cancer Immunol Immunother. 2011 Aug;60(8):1075-84. doi: 10.1007/s00262-011-1021-7. Epub 2011 Apr 26.


Human Vγ2 Vδ2-bearing T cells have recently received much attention in cancer immunotherapy. In this study, we conducted a phase I/II clinical trial of the adoptive transfer of γδ T cells to patients with advanced renal cell carcinoma. Eleven patients who had undergone nephrectomy and had lung metastasis were enrolled. Peripheral blood γδ T cells obtained from the patients were stimulated ex vivo with 2-methyl-3-butenyl-1-pyrophosphate (2M3B1PP), a synthetic pyrophosphomonoester antigen, and transferred in combination with zoledronic acid (Zol) and teceleukin (recombinant human interleukin-2). Expanded γδ T cells exhibited potent cytotoxic activity against tumor cells in vitro, and the proportion of peripheral blood γδ T cells among CD3(+) cells typically peaked three to 5 days after transfer. Tumor doubling time was prolonged in all 11 patients, and the best overall responses were 1 CR, 5 SD, and 5 PD, as defined based on Response Evaluation Criteria in Solid Tumors (RECIST). Although ten patients developed adverse reactions of grade ≥3, they were likely to have been the result of the concomitant infusion of Zol and IL-2, and most symptoms swiftly reverted to normal during the course of treatment. In conclusion, this clinical trial demonstrated that our regimen for the adoptive transfer of γδ T cells in combination with Zol and IL-2 was well tolerated and that objective clinical responses could be achieved in some patients with advanced renal cell carcinoma.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD3 Complex / biosynthesis
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / secondary
  • Carcinoma, Renal Cell / therapy*
  • Cytotoxicity, Immunologic
  • Diphosphonates / administration & dosage
  • Diphosphonates / adverse effects
  • Female
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / adverse effects
  • Immunotherapy, Adoptive*
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / adverse effects
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Organophosphorus Compounds / immunology
  • Organophosphorus Compounds / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology
  • T-Lymphocytes / transplantation
  • Zoledronic Acid


  • 2-methyl-3-butenyl-1-pyrophosphate
  • CD3 Complex
  • Diphosphonates
  • Imidazoles
  • Interleukin-2
  • Organophosphorus Compounds
  • Receptors, Antigen, T-Cell, gamma-delta
  • Zoledronic Acid