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:A CAR-T response prediction model for r/r B-NHL patients based on a T cell subset nomogram.
A CAR-T response prediction model for r/r B-NHL patients based on a T cell subset nomogram.
研究发现,Tc 中 Tcm 与 Tn 的比值能够预测 CD19 CAR-T 细胞在复发/难治性 B-NHL 中的治疗反应。
背景:嵌合抗原受体(CAR)T细胞治疗复发或难治性(r/r)B细胞非霍奇金淋巴瘤(NHL)已显示良好的临床疗效,但影响CAR-T临床应答的因素尚未完全阐明。本研究探讨CD19 CAR-T输注治疗r/r B-NHL疗效的独立影响因素,并建立早期预测模型。 方法:本回顾性研究纳入43例r/r B-NHL患者,记录其一般资料,主要终点为治疗应答。采用单因素和二元Logistic回归分析完全缓解(CR)及部分缓解(PR)的独立影响因素,并据此建立CR概率预测模型。使用受试者工作特征(ROC)曲线和校准图评估模型的区分度和校准度,另收集15名参与者用于模型验证。 结果:43例患者的单因素及二元Logistic回归分析显示,细胞毒性T细胞(Tc)中中央记忆T细胞(Tcm)与初始T细胞(Tn)的比例,是影响r/r B-NHL患者CD19 CAR-T治疗应答的独立危险因素。基于此建立的Tc中Tcm和Tn列线图模型曲线下面积(AUC)为0.914(95% CI:0.832至0.996),敏感度为83%,特异度为74.2%,具有优良预测价值。无进展生存期(PFS)未见差异。 结论:Tc中Tcm和Tn的比例可用于预测r/r B-NHL患者对CD19 CAR-T的治疗应答。我们建立了评估CD19 CAR-T应答的列线图模型,具有较高的特异度和敏感度。
BACKGROUND: Chimeric antigen receptor (CAR) T cells for refractory or relapsed (r/r) B cell no-Hodgkin lymphoma (NHL) patients have shown promising clinical effectiveness. However, the factors impacting the clinical response of CAR-T therapy have not been fully elucidated. We here investigate the independent influencing factors of the efficacy of CD19 CAR-T cell infusion in the treatment of r/r B-NHL and to establish an early prediction model. METHODS: A total of 43 r/r B-NHL patients were enrolled in this retrospective study. The patients' general data were recorded, and the primary endpoint is the patients' treatment response. The independent factors of complete remission (CR) and partial remission (PR) were investigated by univariate and binary logistic regression analysis, and the prediction model of the probability of CR was constructed according to the determined independent factors. Receiver operating characteristic (ROC) and calibration plot were used to assess the discrimination and calibration of the established model. Furthermore, we collected 15 participators to validate the model. RESULTS: Univariate analysis and binary logistic regression analysis of 43 patients showed that the ratio of central memory T cell (Tcm) and na ve T cell (Tn) in cytotoxic T cells (Tc) was an independent risk factor for response to CD19 CAR-T cell therapy in r/r B-NHL. On this basis, the area under the curve (AUC) of Tcm in the Tc and Tn in the Tc nomogram model was 0.914 (95%CI 0.832-0.996), the sensitivity was 83%, and the specificity was 74.2%, which had excellent predictive value. We did not found the difference of the progression-free survival (PFS). CONCLUSIONS: The ratio of Tcm and Tn in Tc was found to be able to predict the treatment response of CD19 CAR-T cells in r/r B-NHL. We have established a nomogram model for the assessment of the CD19 CAR-T therapy response presented high specificity and sensitivity.
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