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:Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Immunogenicity among Chimeric Antigen Receptor T Cell Therapy Recipients.
Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Immunogenicity among Chimeric Antigen Receptor T Cell Therapy Recipients.
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由于基础血液系统恶性肿瘤、既往多线治疗及CAR-T 相关低丙种球蛋白血症等因素,接受CAR-T 细胞治疗的患者可能对严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)疫苗产生体液免疫应答受损。目前针对这一患者群体的疫苗免疫原性综合数据有限。
本研究在单中心开展回顾性分析,纳入接受CD19或BCMA靶向CAR-T 治疗以治疗B细胞非霍奇金淋巴瘤或多发性骨髓瘤的成人患者。患者至少接种2剂BNT162b2或mRNA-1273 SARS-CoV-2疫苗,或1剂Ad26.COV2.S疫苗,并在末次疫苗接种至少1个月后测量抗SARS-CoV-2刺突蛋白抗体(抗S IgG)水平。末次抗S滴度检测前3个月内接受过SARS-CoV-2单克隆抗体治疗或免疫球蛋白的患者予以排除。研究分析血清阳性率(按Roche抗体检测法中抗S检测阈值0.8 U/mL判定)和抗S IgG中位滴度。共纳入50例患者,中位年龄65岁(四分位距[IQR]58–70岁),多数为男性(68%)。32例受试者(64%)产生阳性抗体应答,中位滴度为138.5 U/mL(IQR 11.61–2541 U/mL)。接种3剂疫苗与抗S IgG水平显著较高相关。
本研究支持现行CAR-T 治疗受者SARS-CoV-2疫苗接种指南,并显示完成3剂基础免疫后接种第4剂加强针可提高抗体水平。
然而,滴度总体较低且仍有一定比例患者无应答,表明仍需进一步研究,以优化接种时机并确定该人群疫苗应答的预测因素。
Patients receiving chimeric antigen receptor T cell (CAR-T) therapy may have impaired humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations owing to their underlying hematologic malignancy, prior lines of therapy, and CAR-T-associated hypogammaglobulinemia. Comprehensive data on vaccine immunogenicity in this patient population are limited. A single-center retrospective study of adults receiving CD19 or BCMA-directed CAR-T therapy for B cell non-Hodgkin lymphoma or multiple myeloma was conducted. Patients received at least 2 doses of SARS-CoV-2 vaccination with BNT162b2 or mRNA-1273 or 1 dose of Ad26. COV2.
S and had SARS-CoV-2 anti-spike antibody (anti-S IgG) levels measured at least 1 month after the last vaccine dose. Patients were excluded if they received SARS-CoV-2 monoclonal antibody therapy or immunoglobulin within 3 months of the index anti-S titer. The seropositivity rate (assessed by an anti-S assay cutoff of . 8 U/mL in the Roche assay) and median anti-S IgG titers were analyzed.
Fifty patients were included in the study. The median age was 65 years (interquartile range [IQR], 58 to 70 years), and the majority were male (68%). Thirty-two participants (64%) had a positive antibody response, with a median titer of 138. 5 U/mL (IQR, 11. 61 to 2541 U/mL). Receipt of 3 vaccines was associated with a significantly higher anti-S IgG level.
Our study supports current guidelines for SARS-CoV-2 vaccination among recipients of CAR-T therapy and demonstrates that a 3-dose primary series followed by a fourth booster increases antibody levels.
However, the relatively low magnitude of titers and low percentage of nonresponders demonstrates that further studies are needed to optimize vaccination timing and determine predictors of vaccine response in this population.
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