大剂量IL-2 活化的HLA 半相合异基因造血干细胞治疗10例晚期难治性肾癌的疗效观察*

Efficacy of Large Doses of IL- 2-Activated HLA Haploidentical Peripheral Blood Stem Cells on 10Cases of Refractory Metastatic Renal Cell Carcinoma

  • 摘要: 目的:传统的免疫治疗对晚期难治性肾癌的疗效非常有限,因为肿瘤自身产生了免疫耐受,本研究的目的是探讨大剂量IL- 2 活化的HLA 半相合异基因造血干细胞治疗晚期难治性肾癌的临床疗效。方法:10例晚期肾癌患者以及作为供者的其HLA 半相合的亲属入组。所有患者均接受1 个疗程的haplo-PBSCs 治疗,评估临床疗效和免疫学反应。结果:经IL- 2 活化后获得的HLA 半相合的haplo-PBSCs 总数为(2.3~5.5)× 1010。活化后,NK细胞和活化淋巴细胞亚群(CD69+和CD25+)比例明显升高,而且对肾癌细胞的杀伤活性也明显增强。治疗后,2 例部分缓解(PR),6 例疾病稳定(SD),2 例疾病进展(PD),中位无进展生存期(mPFS)为5.5 个月(3~14个月)。 结论:传统的免疫治疗无效的晚期难治性肾癌患者,采用IL- 2 活化的HLA 半相合异基因造血干细胞治疗可以产生明显的抗肿瘤效应,并且有良好的耐受性。

     

    Abstract: Objective:To evaluate the clinical efficacy of infusion of high-dose interleukin ( IL )- 2-activated allogeneic haploi-dentical peripheral blood stem cells ( haplo-PBSCs ) among patients with advanced intractable renal cell carcinoma ( RCC ). Methods: Ten advanced RCC patients and haploidentical relatives were enrolled as donors for haplo-PBSCs in this treatment. All patients accept-ed one cycle of activated haplo-PBSCs. The clinical and immunologic responses were evaluated. Results: A range from 2.3 to 5.5 ×1010of activated haplo-PBSCs were harvested after exposure to rhIL- 2, along with a significant increase in the proportion of natural killer ( NK ) cells and activated lymphocytes ( CD 69+ and CD 25+ ), and enhanced cytotoxicity of haplo-PBSCs for renal cell carcino -ma. After treatment,2 ( 2/10) cases of partial remission ( PR ), 6 ( 6/10) cases of stable disease ( SD ), and 2 ( 2/10) cases of progres-sive disease ( PD )were identified among the 10patients. The median progression-free survival ( PFS ) of all 10patients was5.5 months ( 3-14months ). Conclusion:The adoptive transfusion of IL- 2-activated haplo-PBSCs can induce sustained anti-tumor effects for advanced intractable RCC patients who do not respond to conventional immunotherapy.

     

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