CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Serial Evaluation of Preimmunization Antibody Titers in Lymphoma Patients Receiving Chimeric Antigen Receptor T Cell Therapy.
Serial Evaluation of Preimmunization Antibody Titers in Lymphoma Patients Receiving Chimeric Antigen Receptor T Cell Therapy.
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抗体滴度及潜在免疫接种需求尚未在CAR-T 细胞治疗(CAR-T)接受者中进行过正式研究。既往研究表明,靶向CD19的CAR-T 可诱导持续性B细胞再生障碍,但保留浆细胞以维持体液免疫应答。为评估CAR-T 接受者的免疫库和抗体滴度状态,我们在罗切斯特梅奥诊所开展了一项针对抗CD19 CAR-T 接受者免疫细胞恢复和疫苗抗体滴度的回顾性研究。在我们的95例CAR-T 接受者队列中,近一半患者在CAR-T 前CD4 T细胞和B细胞计数较低,且在CAR-T 后持续处于低水平。在CAR-T 前,无论既往移植状态如何(CAR-T 后2年内),破伤风血清阴性率最低,肺炎球菌血清阴性率最高。
CAR-T 后3个月时,既往移植组和无既往移植组的总体血清阴性率与CAR-T 前相似。对于接受IVIG的患者,观察到甲型肝炎血清阳性丧失(7例中1例;14%)。肺炎球菌未见血清阳转。对于未接受IVIG的患者,观察到肺炎球菌血清阳性丧失(5例中2例;40%)和甲型肝炎血清阳性丧失(4例中1例;25%)。CAR-T 接受者常出现T细胞和B细胞淋巴细胞减少,尽管补充了IVIG,可能仍缺乏针对疫苗可预防疾病的足够抗体滴度。CAR-T 后抗体滴度可能丧失,凸显了重新接种疫苗的必要性。需要更多具有长期随访的研究来指导CAR-T 后免疫接种的最佳时机。
Antibody titers and the potential need for immunization have not been formally studied in recipients of chimeric antigen receptor T cell therapy (CAR-T). Prior studies have shown that CD19-targeted CAR-T can induce persistent B cell aplasia but preserve plasma cells for humoral response. Aiming to assess the immune repertoire and antibody titer status of CAR-T recipients, we conducted a retrospective study of immune cell recovery and antibody titers to vaccines in anti-CD19 CAR-T recipients at Mayo Clinic, Rochester. In our cohort of 95 CAR-T recipients, almost one-half had low CD4 T and B cell counts prior to CAR-T that remained persistently low post-CAR-T. Prior to CAR-T, the seronegative rate was lowest for tetanus and highest for pneumococcus irrespective of prior transplantation status (within 2 years of CAR-T).
At 3 months post-CAR-T, overall seronegativity rates were similar to pre-CAR-T rates for the prior transplantation and no prior transplantation groups. For patients who received IVIG, loss of seropositivity was seen for hepatitis A (1 of 7; 14%). No seroconversion was noted for pneumococcus. For patients who did not receive IVIG, loss of seropositivity was seen for pneumococcus (2 of 5; 40%) and hepatitis A (1 of 4; 25%).
CAR-T recipients commonly experience T cell and B cell lymphopenia and might not have adequate antibody titers against vaccine-preventable diseases despite IVIG supplementation. Loss of antibody titers post-CAR-T is possible, highlighting the need for revaccination. Additional studies with long-term follow-up are needed to inform the optimal timing of immunization post-CAR-T.
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