PO.IM01.06 · 免疫学

使用特异性多聚体监测CAR-T细胞:一种快速、特异且可实现统一评估的方法

CAR-T-cell monitoring using specific multimers: a fast and specific method allowing uniform evaluation

海报缩略图:使用特异性多聚体监测CAR-T细胞:一种快速、特异且可实现统一评估的方法
编号 4266 展板 2 时间 4/21 09:00–12:00 区域 Section 7 主讲 Alessandra Audia
分会场 CAR T Cell Functional Enhancement
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作者与单位 Authors & Affiliations

Elizabeth Epps1, Kivin Jacobsen2, kevin Lenogue2, Liselotte Brix2

1Immudex, USA LLC, Philadelphia, PA,2Immudex, ApS, Copenhagen, Denmark

摘要 Abstract

中文摘要
CAR-T细胞免疫疗法已成功用于治疗难治性血液系统和实体肿瘤。CAR-T细胞的细胞学监测非常重要,既用于在输注前验证转导T细胞中CAR构建体的表达,也用于监测CAR-T细胞在受者血液中的持久性。CAR表达通常通过针对CAR构建体某一结构部分(而非CAR相互作用的特异性靶标)的荧光素偶联抗体来检测。我们开发了一个灵活的平台,用于制造直接检测CAR-T细胞的多聚体试剂CAR-Dextramer®,可检测不同特异性和亲和力的CAR-T细胞。嵌合抗原受体T(CAR-T)细胞的活化对于确保过继免疫治疗中的疗效至关重要。CAR-T细胞活化需要两个信号:通过CAR的抗原识别和通过细胞内相互作用及白细胞介素等刺激分子的共刺激。控制活化和持续监测对于优化效力、改善血液系统和实体肿瘤免疫治疗的临床结局至关重要。 我们基于CAR-Dextramer®支架开发了含有上述刺激分子的CAR-T细胞活化试剂。这些试剂可用于评估转导的CAR-T细胞通过与其同源靶标的特异性相互作用及共刺激信号被刺激或扩增的能力。
查看英文原文 English abstract
CAR-T cell immunotherapy is used successfully against refractory hematological and solid cancer. Cellular Monitoring of CAR-T cells is important both for validating expression of the CAR construct in the transduced T cells prior to infusion, and persistence of the CAR-T cells in the blood of the recipient. CAR expression is often detected by fluorochrome conjugated antibody against a structural part of the CAR construct, and not the specific target for the CAR interaction. We have developed a flexible platform to manufacture direct CAR-T cells detecting multimer reagents, CAR-Dextramer® allowing detection of CAR-T cells of different specificities and affinities Activation of chimeric antigen receptor T (CAR-T) cells are critical for ensuring therapeutic efficacy in adoptive immunotherapy. CAR-T cell activation requires two signals: antigen recognition through the CAR and co-stimulation via intracellular interactions, and by stimulatory molecules such as interleukins. Control of activation and continuous monitoring are essential to optimize potency to improve clinical outcomes in hematologic and solid tumors immunotherapy. We have developed CAR-T cell activation reagents based on the CAR-Dextramer® scaffold, that contain said stimulatory molecules. These reagents can be used to evaluate the ability of the transduced CAR-T cells to be stimulated or expanded through the specific interaction with its cognate target, and costimulatory signals.
利益披露 Disclosure
E. Epps, None.. K. Jacobsen, None.. K. Lenogue, None.. L. Brix, None.

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