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

H Kobayashi, Y Tanaka, J Yagi, N Minato… - Cancer Immunology …, 2011 - Springer
H Kobayashi, Y Tanaka, J Yagi, N Minato, K Tanabe
Cancer Immunology, Immunotherapy, 2011Springer
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 …
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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