文章：

增强CAR-T细胞：在白血病体内模型中通过植物血凝素激活释放持久影响潜力

Enhancing CAR-T cells: unleashing lasting impact potential with phytohemagglutinin activation in in vivo leukemia model

原文发布日期：2023-12-14 

英文摘要：

Chimeric antigen receptor T (CAR-T) cell therapy holds great promise as an innovative immunotherapeutic approach for cancer treatment. To optimize the production and application of CAR-T cells, we evaluated the in vivo stability and efficacy capacities of CAR-T cells developed under different conditions. In this study, CAR-T cells were activated using Phytohemagglutinin (PHA) or anti-CD3&anti-CD28 and were compared in an in vivo CD19+B-cell cancer model in mouse groups. Our results demonstrated that CAR-T cells activated with PHA exhibited higher stability and anti-cancer efficacy compared to those activated with anti-CD3&anti-CD28. Specifically, CAR19BB-T cells activated with PHA exhibited continuous proliferation and long-term persistence without compromising their anti-cancer efficacy. Kaplan–Meier survival analysis revealed prolonged overall survival in the CAR-T cell-treated groups compared to the only tumor group. Furthermore, specific LTR-targeted RT-PCR analysis confirmed the presence of CAR-T cells in the treated groups, with significantly higher levels observed in the CAR19BB-T (PHA) group compared to other groups. Histopathological analysis of spleen, kidney, and liver tissue sections indicated reduced inflammation and improved tissue integrity in the CAR-T cell-treated groups. Our findings highlight the potential benefits of using PHA as a co-stimulatory method for CAR-T cell production, offering a promising strategy to enhance their stability and persistence. These results provide valuable insights for the development of more effective and enduring immunotherapeutic approaches for cancer treatment. CAR-T cells activated with PHA may offer a compelling therapeutic option for advancing cancer immunotherapy in clinical applications. 

摘要翻译： 

嵌合抗原受体T细胞（CAR-T）疗法作为一种创新的癌症免疫治疗手段具有巨大潜力。为优化CAR-T细胞的生产与应用，我们评估了不同条件下制备的CAR-T细胞的体内稳定性及疗效。本研究采用植物血凝素（PHA）或抗CD3&抗CD28抗体激活CAR-T细胞，并在小鼠CD19+B细胞癌症模型中进行比较。结果显示，与抗CD3&抗CD28激活相比，PHA激活的CAR-T细胞表现出更高的稳定性和抗癌效力。具体而言，PHA激活的CAR19BB-T细胞在保持抗癌效力的同时，呈现持续增殖能力和长期存续特征。Kaplan-Meier生存分析表明，CAR-T细胞治疗组的总生存期较单纯肿瘤组显著延长。此外，特异性LTR靶向RT-PCR分析证实治疗组中存在CAR-T细胞，且CAR19BB-T（PHA）组的细胞水平显著高于其他组别。对脾脏、肾脏和肝脏组织的病理学分析显示，CAR-T细胞治疗组的炎症反应减轻，组织完整性改善。我们的研究结果凸显了PHA作为共刺激方法在CAR-T细胞生产中的潜在优势，为提升细胞稳定性和持久性提供了新策略。这些发现为开发更有效、持久的癌症免疫治疗方法提供了重要参考，表明PHA激活的CAR-T细胞可能为临床癌症免疫治疗的推进提供具有吸引力的治疗选择。

原文链接：

Enhancing CAR-T cells: unleashing lasting impact potential with phytohemagglutinin activation in in vivo leukemia model