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
英文原题:Two-stage inertial microfluidics enrichment of activated T-cells towards a bead-less chimeric antigen receptor manufacturing protocol.
Two-stage inertial microfluidics enrichment of activated T-cells towards a bead-less chimeric antigen receptor manufacturing protocol.
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CAR-T 细胞疗法凭借较高成功率,正在引领癌症细胞免疫治疗领域。然而,CAR-T 细胞制备仍然复杂且成本高昂。利用患者单采起始材料富集T细胞是制备关键步骤,但细胞杂质会干扰T细胞离体转导和增殖。目前包括磁珠分选在内的富集方法存在多种局限。我们报告一种基于惯性微流控、分两阶段完成的无磁珠T细胞富集流程。使用健康供者类似单采的起始样本时,该双阶段流程实现了87%±6%的高效富集和80%±30%的T细胞回收率。使用卵巢癌样本验证该流程,T细胞纯度由起始的48%±6%提高至70%±10%,T细胞回收率为64%±4%。研究还显示,该两阶段惯性微流控流程对细胞增殖没有可检测影响。
CAR-T cell therapy is leading the way in the field of cancer cell immunotherapies due to its high success rates.
However, the manufacturing of CAR-T cells remains complex and expensive. T-cell enrichment from patient apheresis starting material is a key step in the manufacture but cellular impurities interfere with the ex vivo transduction of T-cells and their proliferation. Current enrichment methods including magnetic bead selection suffer from various limitations.
We report here a bead-less T-cell enrichment process through a two-stage procedure based on inertial microfluidics. Using apheresis like starting material samples from healthy donors, the dual-stage process showed an efficient 87% (SD 6%) enrichment and 80% (SD 30%) recovery of T-cells.
Validation of the process with ovarian cancer samples resulted in a T-cell purity 70% (SD 10%) from a starting purity of 48% (SD 6%) at a 64% (SD 4%) T-cell recovery. The two-stage inertial microfluidic process was also shown to have no detectable effect on the proliferation of the cells.
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