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01-08-2011 | Original article

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

Authors: Hirohito Kobayashi, Yoshimasa Tanaka, Junji Yagi, Nagahiro Minato, Kazunari Tanabe

Published in: Cancer Immunology, Immunotherapy | Issue 8/2011

Abstract

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.

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Title: 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
Authors: Hirohito Kobayashi
Yoshimasa Tanaka
Junji Yagi
Nagahiro Minato
Kazunari Tanabe
Publication date: 01-08-2011
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 8/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1021-7

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