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大剂量 IL-2 激活的人白细胞抗原单倍体外周血造血干细胞治疗难治性转移性肾细胞癌的疗效。

Efficacy of large doses of IL-2-activated human leukocyte antigen haploidentical peripheral blood stem cells on refractory metastatic renal cell carcinoma.

机构信息

Biotherapy Center of Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tiyuanbei, Huanhuri Road, Hari District, Tianjin, China.

出版信息

Cancer Biother Radiopharm. 2011 Aug;26(4):503-10. doi: 10.1089/cbr.2011.0982. Epub 2011 Aug 3.

DOI:10.1089/cbr.2011.0982
PMID:21812652
Abstract

Traditional immunotherapy for patients with refractory metastatic renal cell carcinoma (RCC) is limited because the tumors themselves induce immunosuppression. The aim of this article was to evaluate the clinical efficacy of the infusion of a high dose of interleukin (IL)-2-activated allogeneic haploidentical peripheral blood stem cells (haplo-PBSCs) in patients with advanced intractable RCC. Ten advanced RCC patients and their haploidentical relatives, who were haplo-PBSC donors, were enrolled in this study. All patients accepted one cycle of activated haplo-PBSCs. The clinical and immunologic responses were evaluated. A range from 2.3 to 5.5×10(10) of activated haplo-PBSCs were harvested after exposure to recombinant human IL-2 (rhIL-2), along with a significant increase in the proportion of natural killer cells and activated lymphocytes (CD69+ and CD25+). Enhanced cytotoxicity of haplo-PBSCs for RCC was also observed. After treatment, 2 (2/10) cases of partial remission, 6 (6/10) cases of stable disease, and 2 (2/10) cases of progressive disease were identified in these 10 patients. The median progression-free survival of the 10 patients was 5.5 months (3-14 months). The adoptive transfusion of IL-2-activated haplo-PBSCs can induce sustained antitumor effects for advanced intractable RCC patients who have had no response to conventional immunotherapy.

摘要

传统的免疫疗法对难治性转移性肾细胞癌(RCC)患者有限,因为肿瘤本身会诱导免疫抑制。本文旨在评估大剂量白细胞介素(IL)-2 激活的同种异体单倍体外周血干细胞(haplo-PBSC)输注在晚期难治性 RCC 患者中的临床疗效。本研究纳入了 10 例晚期 RCC 患者及其作为 haplo-PBSC 供体的单倍体亲属。所有患者均接受了一个周期的激活 haplo-PBSC 治疗。评估了临床和免疫反应。经过重组人白细胞介素 2(rhIL-2)处理后,收获了 2.3 至 5.5×10(10)个激活的 haplo-PBSC,同时自然杀伤细胞和活化淋巴细胞(CD69+和 CD25+)的比例显著增加。还观察到 haplo-PBSC 对 RCC 的细胞毒性增强。治疗后,这 10 例患者中有 2 例(2/10)部分缓解,6 例(6/10)病情稳定,2 例(2/10)病情进展。10 例患者的中位无进展生存期为 5.5 个月(3-14 个月)。IL-2 激活的 haplo-PBSC 的过继性输注可以诱导对常规免疫疗法无反应的晚期难治性 RCC 患者持续的抗肿瘤作用。

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