决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Enhancing CAR-T cells: unleashing lasting impact potential with phytohemagglutinin activation in in vivo leukemia model.
CAR-T(CAR-T)细胞治疗作为一种创新的癌症免疫治疗手段,具有巨大前景。
CAR-T(CAR-T)细胞疗法作为一种创新性癌症免疫治疗方法,具有巨大前景。为优化CAR-T细胞生产和应用,我们评估了不同条件下制备的CAR-T细胞在体内的稳定性和疗效。本研究中,CAR-T细胞分别采用植物血凝素(PHA)或抗CD3和抗CD28进行活化,并在小鼠CD19+B细胞癌模型中比较。结果显示,与抗CD3和抗CD28活化的细胞相比,PHA活化的CAR-T细胞稳定性更高、抗癌疗效更强。具体而言,PHA活化的CAR19BB-T细胞持续增殖并长期存留,同时未损害其抗癌疗效。Kaplan-Meier生存分析显示,与单纯肿瘤组相比,CAR-T治疗组总生存期延长。此外,针对LTR的特异性RT-PCR分析证实治疗组中存在CAR-T细胞,其中CAR19BB-T(PHA)组水平显著高于其他组。脾、肾和肝组织切片的组织病理学分析显示,CAR-T治疗组炎症减轻、组织完整性改善。研究结果突出显示,PHA作为CAR-T细胞制备的共刺激方法可能具有优势,有望增强其稳定性和持久性。这些结果为开发更有效、持久的癌症免疫治疗方法提供了有价值的见解。PHA活化的CAR-T细胞可能成为推动癌症免疫治疗临床应用的有力治疗选择。
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.
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