输注经照射的HLA部分相合的异基因单个核细胞治疗晚期肾细胞癌

Transfusion of partially HLA-matched irradiated allogeneic blood mononuclear cells for advanced renal-cell carcinoma

背景与目的:肾细胞癌是一种对免疫治疗敏感的肿瘤,包括了非清髓性异基因移植。然而由于严重的毒性,许多转移性肾细胞癌并不适合非清髓性异基因移植。这促使了其他一些新的异基因免疫治疗的发展。本研究评价输注经照射的HLA部分相合的异基因单个核细胞治疗晚期肾细胞癌的有效性和安全性。方法:选择经病理证实的晚期肾细胞癌患者,予输注经照射的HLA部分相合的异基因单个核细胞。每2个月输注1次,治疗有效或稳定者继续输注,直至疾病进展或出现不能耐受的不良反应或患者(或供者)拒绝继续使用。结果:8例患者进入本研究。6例患者每次输注后每日口服沙利度胺100mg至300mg两个月,1例达到持久的完全缓解(CR),5例稳定(SD),2例进展(PD)。8例患者的中位疾病无进展时间为292d,中位生存时间为879d以上。毒性反应轻微。结论:输注经照射的HLA部分相合的异基因单个核细胞治疗晚期肾细胞癌有了一定疗效,值得进一步研究。

Background and purpose：Renal-cell carcinoma（RCC）is susceptible to immune therapy including the use of the nonmyeloablative allogeneic transplantation（NAT）.However,NST can produce severe toxicity,so it might not be appropriate for many patients with metastatic RCC.Other novel allogeneic immunotherapies have been designed to induce an autologous immune response directed against the malignancy.This study evaluated the effi cacy and safety of infusions of partially HLA-matched irradiated allogeneic blood mononuclear cells for advanced renal-cell carcinoma.Methods：Patients with histologically proven diagnosis of advanced RCC received infusions of partially HLA-matched allogeneic blood mononuclear cells.Repeat infusions were given every 8 weeks.Treatment was continued until disease progressed,unacceptable toxicity,or patient（or donor）choice.Results：Eight patients were enrolled.After every infusion,6 patients received an oral administration of thalidomide daily with 100-300 mg/d for 2 months.One patient had durable complete response.Five stable diseases and two progress diseases were observed.In eight patients,time to progression and survival were 320 and 879＋ days,respectively.Severe toxicity was not observed.Conclusion：Infusions of partially HLA-matched irradiated allogeneic blood mononuclear cells for advanced RCC may induce some antitumor effects and deserves further study.