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单倍体相合外周血干细胞治疗复发性/难治性卵巢癌的疗效

Therapeutic effect of haploidentical peripheral blood stem cell treatment on relapsed/refractory ovarian cancer.

作者信息

Li Runmei, Zhang Dong, Ren Baozhu, Cao Shui, Zhou Li, Xiong Yanjuan, Sun Qian, Ren Xiubao

机构信息

National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Tianjin's Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China; Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Tianjin's Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China; Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

出版信息

Bull Cancer. 2023 Mar;110(3):285-292. doi: 10.1016/j.bulcan.2022.11.013. Epub 2023 Feb 2.

Abstract

The traditional immunotherapy is limited on relapsed/refractory metastatic ovarian cancer because tumors cause immunosuppression. Since new therapeutic strategies to improve clinical outcomes for patients with relapsed/refractory metastatic ovarian carcinoma are needed, the aim of this study was to evaluate the therapeutic effect of haploidentical peripheral blood stem cells (haplo-PBSCs) adoptive treatment on relapsed/refractory ovarian cancer. Thirteen patients with advanced stage of ovarian cancer and refractory history after surgery and chemotherapy were treated with interleukin-2 activated haplo-PBSCs donated by their parents or children. Clinical outcomes including therapeutic response by measuring tumor size changes using CT scanning, CA-125 levels and survival times were evaluated. T and NK cell population in patients before and after treatment was detected by flow cytometry analysis. The median follow-up time after haplo-PBSCs adoptive treatment was 14 months. At the time of the last follow-up, the median overall survival after haplo-PBSCs adoptive treatment was 9.1 months. Ten patients (76.9%) achieved a relief of symptoms, including abdominal distention, ache, fatigue, and poor appetite. During the first 2 months after treatment, CA125 levels decreased in 10 patients (76.9%). Five patients (38.5%) had a stable disease and 1 patient (8%) had partial response. T cell population (CD3CD4 and CD3CD8) and CD3CD16CD56 NK cells were increased in patients after haplo-PBSCs adoptive treatment. Our study reveals that haplo-PBSCs adoptive treatment is associated with an anti-tumor effect and increasing immune responses in patients with relapsed/refractory ovarian cancer.

摘要

传统免疫疗法在复发性/难治性转移性卵巢癌治疗中存在局限性,因为肿瘤会导致免疫抑制。由于需要新的治疗策略来改善复发性/难治性转移性卵巢癌患者的临床结局,本研究旨在评估单倍体相合外周血干细胞(haplo-PBSCs)过继性治疗对复发性/难治性卵巢癌的治疗效果。13例卵巢癌晚期且术后及化疗后难治的患者接受了由其父母或子女捐献的经白细胞介素-2激活的单倍体相合外周血干细胞治疗。通过CT扫描测量肿瘤大小变化、CA-125水平和生存时间等临床结局来评估治疗反应。采用流式细胞术分析检测患者治疗前后的T细胞和NK细胞群体。单倍体相合外周血干细胞过继性治疗后的中位随访时间为14个月。在最后一次随访时,单倍体相合外周血干细胞过继性治疗后的中位总生存期为9.1个月。10例患者(76.9%)症状得到缓解,包括腹胀、疼痛、疲劳和食欲不佳。治疗后的前2个月内,10例患者(76.9%)的CA125水平下降。5例患者(38.5%)病情稳定,1例患者(8%)有部分缓解。单倍体相合外周血干细胞过继性治疗后患者的T细胞群体(CD3CD4和CD3CD8)以及CD3CD16CD56 NK细胞增加。我们的研究表明,单倍体相合外周血干细胞过继性治疗对复发性/难治性卵巢癌患者具有抗肿瘤作用并能增强免疫反应。

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