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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Optimizing the timing of lymphocyte collection after stem cell harvesting in B-cell lymphoma and myeloma patients.
Optimizing the timing of lymphocyte collection after stem cell harvesting in B-cell lymphoma and myeloma patients.
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与从接受过大量治疗的复发患者中采集淋巴细胞相比,在干细胞采集后立即采集淋巴细胞可维持良好的 T 细胞特性。该方法利用现有血管通路,同时最大限度地减轻患者负担,提供了一种实用且具有成本效益的策略。我们的研究结果支持将采集后淋巴细胞采集整合入高危患者的 T 细胞治疗方案,以改善结局并简化诊疗流程。
高质量的 T 细胞单采产品对于嵌合抗原受体 (CAR) T 细胞疗法等细胞疗法的成功至关重要。然而,CAR-T 细胞疗法通常适用于复发/难治性 B 细胞淋巴瘤和多发性骨髓瘤患者,其中重复化疗会耗尽初始干细胞和 T 记忆干细胞亚群,并增加 T 细胞耗竭。早期淋巴细胞收集(理想情况是在广泛化疗之前)可以提高 T 细胞质量并改善治疗结果。
本研究评估了 B 细胞淋巴瘤或多发性骨髓瘤患者在自体干细胞收获后立即收集淋巴细胞的可行性。我们分析了 25 名高危淋巴瘤和骨髓瘤患者的 T 细胞表型和基因表达谱,使用流式细胞术和 RNA 测序将动员化疗前收集的样本与干细胞收获后收集的样本进行比较。评估了与 T 细胞分化和耗竭相关的关键标志物。
收获后淋巴细胞显示效应记忆 T 细胞、程序性细胞死亡蛋白 1 表达和调节性 T 细胞适度增加,同时 CD4+ 初始 T 细胞/T 记忆干细胞略有减少。转录组分析显示两个时间点之间没有显着差异。尽管免疫表型的变化具有统计学显着性,但变化较小(<5%)。
This study evaluated the feasibility of collecting lymphocytes immediately after autologous stem cell harvesting in patients with B-cell lymphoma or multiple myeloma. We analyzed T-cell phenotypes and gene expression profiles from 25 high-risk lymphoma and myeloma patients, comparing samples collected before mobilization chemotherapy with those collected after stem cell harvesting using flow cytometry and RNA sequencing. Key markers related to T-cell differentiation and exhaustion were assessed.
Post-harvest lymphocytes showed a modest increase in effector memory T cells, programmed cell death protein 1 expression and regulatory T cells along with a slight decrease in CD4+ naive T cells/T memory stem cells. Transcriptome analysis revealed no significant differences between the two time points. Although changes in immunophenotyping were statistically significant, they were minor (<5%).
Collection of lymphocytes immediately after stem cell harvesting maintains favorable T-cell characteristics compared with collection from heavily treated relapsed patients. This approach offers a practical and cost-effective strategy using existing vascular access while minimizing patient burden. Our findings support integrating post-harvest lymphocyte collection into T-cell therapy protocols for high-risk patients to improve outcomes and streamline care.
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