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AIM平台:一种基于新型纳米人工抗原呈递细胞的临床系统,旨在持续生产具有强大且持久抗肿瘤特性的多抗原特异性T细胞产品。

AIM Platform: A Novel Nano Artificial Antigen-Presenting Cell-Based Clinical System Designed to Consistently Produce Multi-Antigen-Specific T-Cell Products with Potent and Durable Anti-Tumor Properties.

作者信息

Suarez Lauren, Wang Ruipeng, Carmer Scott, Bednarik Daniel, Myint Han, Jones Kristi, Oelke Mathias

机构信息

NexImmune, Gaithersburg, Maryland, USA.

出版信息

Transfus Med Hemother. 2020 Dec;47(6):464-471. doi: 10.1159/000512788. Epub 2020 Nov 16.

Abstract

Over the last decade, tremendous progress has been made in the field of adoptive cell therapy. The two prevailing modalities include endogenous non-engineered approaches and genetically engineered T-cell approaches. Endogenous non-engineered approaches include dendritic cell-based systems and tumor-infiltrating lymphocytes (TIL) that are used to produce multi-antigen-specific T-cell products. Genetically engineered approaches, such as T-cell receptor engineered cells and chimeric antigen receptor T cells are used to produce single antigen-specific T-cell products. It is noted by the authors that there are alternative methods to sort for antigen-specific T cells such as peptide multimer sorting or cytokine secretion assay-based sorting, both of which are potentially challenging for broad development and commercialization. In this review, we are focusing on a novel nanoparticle technology that generates a non-engineered product from the endogenous T-cell repertoire. The most common approaches for ex vivo activation and expansion of endogenous, non-genetically engineered cell therapy products rely on dendritic cell-based systems or IL-2 expanded TIL. Hurdles remain in developing efficient, consistent, controlled processes; thus, these processes still have limited access to broad patient populations. Here, we describe a novel approach to produce cellular therapies at clinical scale, using proprietary nanoparticles combined with a proprietary manufacturing process to enrich and expand antigen-specific CD8 T-cell products with consistent purity, identity, and composition required for effective and durable anti-tumor response.

摘要

在过去十年中,过继性细胞疗法领域取得了巨大进展。两种主要的方式包括内源性非工程化方法和基因工程T细胞方法。内源性非工程化方法包括基于树突状细胞的系统和用于产生多抗原特异性T细胞产物的肿瘤浸润淋巴细胞(TIL)。基因工程方法,如T细胞受体工程化细胞和嵌合抗原受体T细胞,用于产生单抗原特异性T细胞产物。作者指出,存在其他分选抗原特异性T细胞的方法,如肽多聚体分选或基于细胞因子分泌测定的分选,这两种方法对于广泛的开发和商业化都可能具有挑战性。在本综述中,我们关注一种新型纳米颗粒技术,该技术可从内源性T细胞库中产生非工程化产物。用于内源性、非基因工程化细胞治疗产品体外激活和扩增的最常见方法依赖于基于树突状细胞的系统或IL-2扩增的TIL。在开发高效、一致、可控的工艺方面仍然存在障碍;因此,这些工艺仍然只能有限地应用于广大患者群体。在此,我们描述了一种在临床规模上生产细胞疗法的新方法,即使用专利纳米颗粒结合专利制造工艺,以富集和扩增具有有效和持久抗肿瘤反应所需的一致纯度、同一性和组成的抗原特异性CD8 T细胞产物。

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