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:Humoral vaccine responses following Chimeric Antigen Receptor T-cell therapy for hematological malignancies.
共纳入 73 例在 pre- 或 post- 滴度检测前八周内未接受静脉注射免疫球蛋白的患者。
这项单中心回顾性研究分析了2018年至2024年间接受嵌合抗原受体(CAR)T细胞治疗后接种疫苗的患者的疫苗反应。疫苗接种按照EBMT/CIBMTR推荐进行,并评估了对12种疫苗可预防感染的病原体特异性IgG反应。血清保护定义为已确定的临界值或滴度显著倍数增加。共纳入73例在接种前或接种后滴度检测前八周内未接受静脉注射免疫球蛋白的患者。疫苗接种开始的中位时间为CAR T后13个月(范围6-66)。49例患者有接种前和接种后滴度数据。破伤风和脊髓灰质炎病毒的接种前血清保护率高(> 85%)。在接种前未获得血清保护的患者中,破伤风和脊髓灰质炎的疫苗反应率高(100%),白喉(75%)和b型流感嗜血杆菌(62%)为中等,百日咳(48%)、甲型肝炎(43%)、乙型肝炎(44%)和肺炎球菌病(33%)较低。CD19 CAR T接受者的接种前血清保护率高于BCMA接受者,但两组之间的疫苗反应无显著差异。接种前IgA水平与疫苗反应显著相关,应答者中绝对B细胞计数有升高趋势(p = 0.054)。我们的发现强调了免疫重建在CAR T后疫苗反应中的重要性。
This single-center, retrospective study analyzed vaccine responses in patients who received post-Chimeric Antigen Receptor (CAR) T-cell therapy vaccination between 2018 and 2024. Vaccinations were administered according to EBMT/CIBMTR recommendations and pathogen-specific IgG responses to 12 vaccine-preventable infections were assessed. Seroprotection was defined by established cut-offs or a significant fold increase in titers. A total of 73 patients that had not received intravenous immunoglobulins within the eight weeks prior to pre- or post titer were included. The median time to vaccination initiation was 13 months (range 6-66) post-CAR T. Pre and post-vaccination titers were available for 49 patients. Pre-vaccination seroprotection was high (> 85%) for tetanus and poliovirus. Among patients not seroprotected prior to vaccination, vaccine response rates were high for tetanus and polio (100%), moderate for diphtheria (75%) and haemophilus influenzae type b (62%), and lower for pertussis (48%), hepatitis A (43%), hepatitis B (44%), and pneumococcal disease (33%). CD19 CAR T recipients had higher pre-vaccination seroprotection rates than BCMA recipients, but vaccine responses did not differ significantly between groups. Pre-vaccination IgA levels were significantly associated with vaccine response, and absolute B-cell counts trended higher among responders (p = 0.054). Our findings highlight the importance of immune reconstitution in vaccine responses post-CAR T.
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