Cyclophosphamide-using nonmyeloablative allogeneic cell therapy against renal cancer with a reduced risk of graft-versus-host disease
Cyclophosphamide-using nonmyeloablative allogeneic cell therapy against renal cancer with a reduced risk of graft-versus-host disease
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DOI：
10.1158/1078-0432.ccr-06-1578
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发表时间：
2007-02-01
影响因子：
11.5
通讯作者：
Naito, Seiji
中科院分区：
文献类型：
--
作者：
Eto, Masatoshi;Harano, Masahiko;Naito, Seiji
目的：非清髓性异体干细胞移植治疗肾癌已引起广泛关注。我们最近提出了一种使用环磷酰胺的非清髓细胞疗法，在对供体细胞进行耐受性诱导后进行供体淋巴细胞输注（DLI）。在考虑使用环磷酰胺的细胞疗法的临床应用时，试图减少移植物抗宿主病（GVHD）是至关重要的。本研究的目的是改进使用环磷酰胺的细胞疗法，以降低GVHD的风险，同时保持对肾癌的抗肿瘤活性。实验设计：我们评估了在环磷酰胺治疗后第1天至第5天延迟进行DLI是否可以降低GVHD的风险，同时在使用环磷酰胺的细胞治疗中保持对RENCA（一种小鼠致癌物质诱导的肾细胞癌）的抗肿瘤活性。结果：在体内抗肿瘤效果方面，环磷酰胺治疗后第1天与第5天DLI无差异，而小肠组织学结果显示，环磷酰胺使用细胞治疗第5天DLI降低了GVHD的风险。此外，在第5天给予DLI治疗的RENCA排斥小鼠中也观察到对RENCA的获得性免疫。结论：我们的研究结果表明，在使用环磷酰胺的非清髓细胞治疗期间延迟DLI可以通过降低GVHD的风险来分离移植物抗肿瘤效应。
Purpose: Much attention has been paid to nonmyeloablative allogeneic stem cell transplantation for the treatment of renal cancer. We recently proposed a cyclophosphamide-using nonmyeloablative cell therapy in which donor lymphocyte infusion (DLI) was carried out after the tolerance induction to donor cells. In considering the clinical application of the cyclophosphamide-using cell therapy, attempts to reduce graft-versus-host disease (GVHD) are crucial. The aim of the present study was to modify the cyclophosphamide-using cell therapy to reduce the risk of GVHD while preserving the antitumor activity against renal cancer.Experimental Design: We assessed whether a delay in performing DLI from day 1 to day 5 after the cyclophosphamide treatment could reduce the risk of GVHD while preserving antitumor activity against RENCA, a murine carcinogen-induced renal cell carcinoma, in the cyclophosphamide-using cell therapy.Results: Regarding the in vivo antitumor effect, there was no difference between DLI on day 1 and day 5 after the cyclophosphamide treatment, whereas the histologic findings of the small intestine showed that the cyclophosphamide-using cell therapy with DLI on day 5 decreased the risk of GVHD. In addition, the acquired immunity against RENCA was also observed in the RENCA-rejected mice that had been treated with DLI on day 5.Conclusions: Our results show that a delay in DLI during cyclophosphamide-using nonmyeloablative cell therapy can dissociate graft-versus-tumor effects from GVHD by reducing the risk of GVHD.