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 and T-cell immune responses to coronavirus disease 2019 vaccines in patients with hematological malignancies.
本研究提供了确证性真实世界证据,表明CD19恢复是体液应答的关键决定因素,而疫苗诱导的T细胞免疫即使在抗体无应答者中也可能得以保留,支持在这一高风险人群中继续开展疫苗接种工作。
背景:近期研究显示,血液系统恶性肿瘤(HM)患者接种2019冠状病毒病(COVID-19)疫苗后体液免疫应答显著受损。尽管加强针和细胞免疫应答日益受到关注,但很少有研究同时评估接受苯达莫司汀、双特异性抗体或CAR-T治疗患者的体液和细胞免疫。本研究旨在评估接受免疫化疗或新型药物治疗的B细胞淋巴瘤患者接种COVID-19疫苗后的体液免疫原性、T细胞免疫应答和加强针效果。方法:在第二剂和加强(第三)剂mRNA疫苗接种后检测血清SARS-CoV-2刺突蛋白抗体(S-IgG),并采用酶联免疫斑点法检测特异性T细胞应答。结果:114例患者中有46例(40%)产生抗体。年龄<65岁(比值比8.99)和CD19水平达到50/μL(比值比19.7)是应答的独立预测因素。受试者工作特征曲线分析支持该阈值的选择,并确认尽管统计学最佳截点较低,CD19 50/μL仍是具有临床意义的区分界值。部分未产生抗体的患者仍可检测到T细胞应答(两剂后36%;加强针后45.5%)。加强针提高了抗体应答率(40%升至62.9%)和T细胞应答率(47.2%升至57.6%)。结论:本研究提供了真实世界的验证性证据,表明CD19恢复是体液应答的关键决定因素;即使抗体无应答者也可能保留疫苗诱导的T细胞免疫,支持继续为这一高危人群接种疫苗。
BACKGROUND: Recent studies have demonstrated that patients with hematological malignancies (HM) exhibit significantly impaired humoral immune responses after coronavirus disease 2019 (COVID-19) vaccination. Although booster doses and cellular immune responses have been increasingly studied, few analyses have concurrently evaluated both humoral and cellular immunity in patients receiving bendamustine, bispecific antibodies, or CAR-T therapies. We aimed to assess the humoral immunogenicity, T-cell immune response, and booster effect after COVID-19 vaccination in patients with B-cell lymphoma undergoing immunochemotherapy or novel agent treatment. METHODS: Serum antibodies to the severe acute respiratory syndrome coronavirus 2 spike protein (S-IgG) were measured after the second and booster (third) mRNA vaccinations, and specific T-cell responses were measured using the enzyme-linked immunosorbent spot method. RESULTS: Forty-six of 114 patients (40%) acquired antibodies. Age < 65 years (odds ratio 8.99) and CD19 50/ L (odds ratio 19.7) were independent predictors of response. To support the selection of this threshold, operating characteristic curve analysis was performed and confirmed CD19 50/ L as a clinically meaningful discriminator despite a lower statistical cutoff. Even in some patients who did not develop antibodies, T-cell responses were observed (36% after two doses; 45.5% after the booster). The booster vaccine enhanced antibody (40% to 62.9%) and T-cell (47.2% to 57.6%) responses. CONCLUSIONS: This study provides confirmatory real-world evidence that CD19 recovery is a key determinant of humoral response, while vaccine-induced T-cell immunity may be preserved even in antibody-nonresponders, supporting continued vaccination efforts in this high-risk population.
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