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
一种用于嵌合抗原受体（CAR）T 细胞产品功能评估的新型多色荧光斑点试验
英文原题：A novel multicolor fluorescent spot assay for the functional assessment of chimeric antigen receptor (CAR) T-cell products.
查看英文原题
A novel multicolor fluorescent spot assay for the functional assessment of chimeric antigen receptor (CAR) T-cell products.
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研究概要
我们开发了一种用于 CAR-T 产品定量和功能性效力评估的新型检测方法。我们优化的 MFSA 具有成本效益、易于操作、可靠，可过夜完成，从而能够将产品快速交付给患者，并且所需的维护和培训相对较少。我们这种新型检测方法的临床价值将在一项前瞻性研究中评估，该研究将 CAR-T 产品的输注前评估与患者的结局相关联。
研究思路结论见上方概要
背景
嵌合抗原受体（CAR）T细胞（CAR-T）疗法已经彻底改变了B细胞淋巴瘤的治疗。遗憾的是，靶向CD19的CAR-T 治疗后复发相对常见，因此，亟需能够在输注前评估CAR-T 产品功能和效力的检测方法，这有望帮助优化CAR-T 疗法。我们开发了一种新型多色荧光斑点检测法（MFSA），用于在单细胞水平上对CAR-T 产品进行功能评估，将CAR-T 产品的数量评估与其功能表征相结合。
方法
我们首先使用标准的单细胞干扰素（IFN）-酶联免疫吸附斑点试验来测量CD19靶向CAR-T 对CD19包被珠的应答。随后，我们开发、优化并验证了一种MFSA，可在单个CAR-T 水平上同时测量不同细胞因子组合的分泌。
结果
我们将IFN-/肿瘤坏死因子-/颗粒酶B确定为最相关的细胞因子组合，并使用我们的新型MFSA对两种临床级CAR-T 产品进行了功能和数值表征。
展开英文摘要原文
METHODS
We first used a standard single-cell interferon (IFN)- enzyme-linked immune absorbent spot assay to measure CD19-targeted CAR-T responses to CD19-coated beads. We then developed, optimized and validated an MFSA that simultaneously measures the secretion of combinations of different cytokines on a single CAR-T level.
RESULTS
We identified IFN- /tumor necrosis factor- /granzyme B as the most relevant cytokine combination, and we used our novel MFSA to functionally and numerically characterize two clinical-grade CAR-T products.
CONCLUSIONS
In conclusion, we have developed a novel assay for the quantitative and functional potency assessment of CAR-T products. Our optimized MFSA is cost-effective, easy to perform, reliable, can be performed overnight, allowing for a fast delivery of the product to the patient, and requires relatively minimal maintenance and training. The clinical value of our novel assay will be assessed in studies correlating the pre-infusion assessment of CAR-T products with the patients' outcome in a prospective fashion.
论文信息
- 作者
- Atanackovic D、Iraguha T、Omili D、Avila SV、Fan X、Kocoglu M、Gebru E、Baker JM
- 单位
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA; Transplant and Cellular Therapy Program, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA; Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland, USA. Electronic address: datanackovic@som.umaryland.edu.United States
- 文献类型
- 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Cytotherapy2024 Apr
- 原文标识
- PubMed 38340107 · DOI 10.1016/j.jcyt.2024.01.006