CD20
CD19
嵌合抗原受体
淋巴瘤
免疫学
免疫疗法
癌症的体细胞进化
抗原
癌症研究
生物
医学
内科学
癌症
免疫系统
作者
Johannes Duell,Alexander Leipold,Silke Appenzeller,Viktoria Fuhr,Hilka Rauert‐Wunderlich,Matteo Da Viá,Oliver Dietrich,Christophe Toussaint,Fabian Imdahl,Florian Eisele,Nazia Afrin,Lars Grundheber,Hermann Einsele,Niels Weinhold,Andreas Rosenwald,Max S. Topp,Antoine‐Emmanuel Saliba,Leo Rasche
出处
期刊:Blood
[American Society of Hematology]
日期:2024-02-22
卷期号:143 (8): 685-696
被引量:10
标识
DOI:10.1182/blood.2023021672
摘要
Abstract CD19 chimeric antigen receptor (CAR) T cells and CD20 targeting T-cell–engaging bispecific antibodies (bispecs) have been approved in B-cell non-Hodgkin lymphoma lately, heralding a new clinical setting in which patients are treated with both approaches, sequentially. The aim of our study was to investigate the selective pressure of CD19- and CD20-directed therapy on the clonal architecture in lymphoma. Using a broad analytical pipeline on 28 longitudinally collected specimen from 7 patients, we identified truncating mutations in the gene encoding CD20 conferring antigen loss in 80% of patients relapsing from CD20 bispecs. Pronounced T-cell exhaustion was identified in cases with progressive disease and retained CD20 expression. We also confirmed CD19 loss after CAR T-cell therapy and reported the case of sequential CD19 and CD20 loss. We observed branching evolution with re-emergence of CD20+ subclones at later time points and spatial heterogeneity for CD20 expression in response to targeted therapy. Our results highlight immunotherapy as not only an evolutionary bottleneck selecting for antigen loss variants but also complex evolutionary pathways underlying disease progression from these novel therapies.
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