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来自异基因造血细胞移植后植入患者的全嵌合 CAR.CIK:跨主要人类白细胞抗原屏障的可行性、抗白血病潜力和同种反应性

英文原题:Full chimaeric CAR.CIK from patients engrafted after allogeneic haematopoietic cell transplant: Feasibility, anti-leukaemic potential and alloreactivity across major human leukocyte antigen barriers.

查看英文原题

Full chimaeric CAR.CIK from patients engrafted after allogeneic haematopoietic cell transplant: Feasibility, anti-leukaemic potential and alloreactivity across major human leukocyte antigen barriers.

PubMed 2022/09/26(内容时间) Br J Haematol Q2 · IF 3.6(JCR 2025)

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中文摘要

细胞因子诱导的杀伤淋巴细胞(CIK)因其固有的抗肿瘤活性和较低的移植物抗宿主病(GVHD)风险,是异基因造血细胞移植(HCT)后传统供者淋巴细胞输注(DLI)的一种有前景的替代方案。我们探索了从全供者嵌合(fc)患者中生成并经嵌合抗原受体(CAR)基因重定向靶向白血病靶点CD44v6的CIK(fcCAR.CIK)的可行性、抗白血病活性和异体反应风险。fcCAR.CIK成功从HCT后完全缓解的白血病患者中体外扩增,证实了其强烈的临床前抗白血病活性,且未增强跨人类白细胞抗原(HLA)屏障的异体反应性。我们的研究为支持fcCAR.CIK的临床研究提供了转化基础,fcCAR.CIK是一种介于自体与异体来源之间的生物学桥梁,可作为HCT后DLI的替代方案。

展开英文摘要原文

Cytokine-induced killer lymphocytes (CIK) are a promising alternative to conventional donor lymphocyte infusion (DLI), following allogeneic haematopoietic cell transplantation (HCT), due to their intrinsic anti-tumour activity and reduced risk of graft-versus-host disease (GVHD).

We explored the feasibility, anti-leukaemic activity and alloreactive risk of CIK generated from full-donor chimaeric (fc) patients and genetically redirected by a chimeric antigen receptor (CAR) (fcCAR. CIK) against the leukaemic target CD44v6. fcCAR. CIK were successfully ex-vivo expanded from leukaemic patients in complete remission after HCT confirming their intense preclinical anti-leukaemic activity without enhancing the alloreactivity across human leukocyte antigen (HLA) barriers.

Our study provides translational bases to support clinical studies with fcCAR. CIK, a sort of biological bridge between the autologous and allogeneic sources, as alternative DLI following HCT.

论文信息

作者
Circosta P、Donini C、Gallo S、Giraudo L、Gammaitoni L、Rotolo R、Galvagno F、Capellero S
第一作者单位
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.Italy
通讯作者单位
Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.Italy
文献类型
非美国政府资助研究
期刊
British journal of haematology2023 Jan
原文标识
PubMed 36155897 · DOI 10.1111/bjh.18469