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
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
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DOI：
10.1007/s00262-011-1021-7
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发表时间：
2011-08-01
影响因子：
5.8
通讯作者：
Tanabe, Kazunari
中科院分区：
文献类型：
--
作者：
Kobayashi, Hirohito;Tanaka, Yoshimasa;Tanabe, Kazunari
人类携带V γ 2v δ 2的T细胞近年来在肿瘤免疫治疗中受到广泛关注。在这项研究中，我们对晚期肾细胞癌患者进行了γ δ T细胞过继转移的I/II期临床试验。11例行肾切除术并有肺转移的患者被纳入研究。在体外用2-甲基-3-丁烯基-1-焦磷酸（2M3B1PP）（一种合成焦磷酸单酯抗原）刺激患者外周血γ δ T细胞，并与唑来膦酸（Zol）和重组人白细胞介素-2 （teceleukin）联合转移。扩增的γ δ T细胞在体外对肿瘤细胞表现出强大的细胞毒活性，在CD3（+）细胞中，外周血γ δ T细胞的比例通常在转移后3至5天达到峰值。所有11例患者的肿瘤倍增时间均延长，根据实体肿瘤反应评价标准（RECIST），最佳总缓解为1 CR， 5 SD和5 PD。虽然有10例患者出现了千分之一a级不良反应3，但它们很可能是同时输注Zol和IL-2的结果，大多数症状在治疗过程中迅速恢复正常。总之，这项临床试验表明，我们的伽马δ T细胞过继转移联合Zol和IL-2方案耐受性良好，并且在一些晚期肾细胞癌患者中可以实现客观的临床反应。
Human V gamma 2 V delta 2-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 gamma delta T cells to patients with advanced renal cell carcinoma. Eleven patients who had undergone nephrectomy and had lung metastasis were enrolled. Peripheral blood gamma delta 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 gamma delta T cells exhibited potent cytotoxic activity against tumor cells in vitro, and the proportion of peripheral blood gamma delta 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 a parts per thousand yen3, 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 gamma delta 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.