CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CD25/CD71 同种异体清除 T 细胞免疫治疗以改善匹配无关供者造血干细胞移植后 T 细胞重建：一项随机试验
英文原题：Immunotherapy with CD25/CD71-allodepleted T cells to improve T-cell reconstitution after matched unrelated donor hematopoietic stem cell transplant: a randomized trial.
查看英文原题
Immunotherapy with CD25/CD71-allodepleted T cells to improve T-cell reconstitution after matched unrelated donor hematopoietic stem cell transplant: a randomized trial.
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研究概要
这些数据表明，过继转移 ADTs 是安全的，但在 MUD 情况下，其在 T 细胞重建方面的益处有限。这种方法在更严格的 T 细胞清除背景下可能更有用。
研究思路结论见上方概要
背景
延迟的免疫重建是匹配无关供者（MUD）干细胞移植（SCT）后的主要挑战。在这项随机2期多中心试验中，即采用CD25/71同种异体去除供者T细胞过继免疫治疗以改善无关供者干细胞移植后免疫（NCT01827579），作者测试了同种异体去除供者T细胞（ADTs）是否可以安全地用于改善基于阿仑单抗的MUD SCT治疗血液恶性肿瘤后的免疫重建。
方法
患者接受标准治疗或最多三剂递增剂量的ADTs，这些ADTs通过CD25+/CD71+免疫磁珠去除法生成。研究的主要终点是SCT后4个月时的循环CD3+ T细胞计数。共有21名患者接受治疗，其中13名在ADT组，8名在对照组。
结果
作者观察到，与对照组相比，ADT组在4个月时CD3+ T细胞计数有改善趋势（230/µL vs 145/µL，P = 0.18），并且有3例ADT患者在4个月时达到正常CD3+ T细胞计数（>700/µL）。两组的显著移植物抗宿主病（GVHD）发生率相当，ADT组和对照组分别有7/13和4/8例患者发生≥2级急性GVHD，分别有3/13和3/8例患者发生慢性GVHD。
展开英文摘要原文
METHODS
Patients received standard of care or up to three escalating doses of ADTs generated through CD25+/CD71+ immunomagnetic depletion. The primary endpoint of the study was circulating CD3+ T-cell count at 4 months post-SCT. Twenty-one patients were treated, 13 in the ADT arm and eight in the control arm.
RESULTS
The authors observed a trend toward improved CD3+ T-cell count at 4 months in the ADT arm versus the control arm (230/µL versus 145/µL, P = 0.18), and three ADT patients achieved normal CD3+ T-cell count at 4 months (>700/µL). The rates of significant graft-versus-host disease (GVHD) were comparable in both cohorts, with grade ≥2 acute GVHD in seven of 13 and four of eight patients and chronic GVHD in three of 13 and three of eight patients in the ADT and control arms, respectively.
CONCLUSIONS
These data suggest that adoptive transfer of ADTs is safe, but that in the MUD setting the benefit in terms of T-cell reconstitution is limited. This approach may be of more use in the context of more rigorous T-cell depletion.
论文信息
- 作者
- Peggs KS、Albon SJ、Oporto Espuelas M、Irving C、Richardson R、Casanovas-Company J、Wallace R、Guvenel A
- 第一作者单位
- Department of Hematology, University College London Hospital, London, UK.United Kingdom
- 通讯作者单位
- Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, UK; Department of Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, UK. Electronic address: persis.amrolia@gosh.nhs.uk.United Kingdom
- 文献类型
- 随机对照试验 · 多中心研究 · II 期临床试验 · 非美国政府资助研究
- 期刊
- Cytotherapy2023 Jan
- 原文标识
- PubMed 36220712 · DOI 10.1016/j.jcyt.2022.08.010