Suppr超能文献

使用无细胞人工靶颗粒对 CAR-T 细胞进行标准化评估。

Standardized evaluation of CAR-T cells using acellular artificial target particles.

机构信息

Refuge Biotechnologies, Menlo Park, CA, United States.

Biotechnology Science and Engineering, The University of Alabama in Huntsville, Huntsville, AL, United States.

出版信息

Front Immunol. 2022 Oct 20;13:994532. doi: 10.3389/fimmu.2022.994532. eCollection 2022.

Abstract

The horizon of immunotherapy using CAR-T cells is continuously extending to treat solid tumors beyond the success in the treatment of liquid tumors. Precise evaluations of CAR-T cells for their phenotypes, quantity and quality of activation in various tumor microenvironments including different antigen densities, and the resulting effector functions are critical for the successful development of CAR-T therapies and safe translation to clinics. Unfortunately, the development of methods and tools to accommodate these needs have been lagging behind. Here, we developed a novel biomaterial platform, acellular artificial target particles (aaTPs) against CAR-T cells, using magnetic microbeads that are already widely employed in the manufacturing of T cell products. By devising a simple and standardized procedure, we precisely controlled the antigen surface densities presented on the aaTPs for a wide range. By co-incubation of aaTPs with CAR-T cells followed by flow cytometry and cytokine assays, we quantitatively determined the antigen-specific and dose-dependent activation of anti-HER2 CAR-T cells. We also demonstrated that the aaTP can serve as a clean target cell in assays to prove the proposed mechanism of action of a next-generation CAR-T product. Overall, the simple, inexpensive, modular and precisely controllable synthetic nature of aaTPs enables the development of clean and standardized assays for CAR-T cells, which provides critical advantages over the conventional assays using target cell lines. The design of aaTPs can be extended to include other tumor antigens and relevant surface molecules of physiological target cells. Thus, the aaTP platform has great potential as a standardized tool for the development and evaluation of both conventional and new CAR-T products in the context of approval from regulatory agencies and clinical translation.

摘要

嵌合抗原受体 T 细胞(CAR-T)免疫疗法的应用范围不断扩大,除了在治疗液体肿瘤方面取得成功外,还开始应用于治疗实体瘤。精确评估 CAR-T 细胞在各种肿瘤微环境(包括不同抗原密度)中的表型、激活数量和质量以及由此产生的效应功能,对于成功开发 CAR-T 疗法并安全转化为临床应用至关重要。不幸的是,适应这些需求的方法和工具的发展一直滞后。在这里,我们开发了一种新型生物材料平台,即针对 CAR-T 细胞的无细胞人工靶粒子(aaTP),使用已经广泛应用于 T 细胞产品制造的磁性微珠。通过设计一种简单且标准化的程序,我们精确控制 aaTP 上呈现的抗原表面密度在很宽的范围内。通过将 aaTP 与 CAR-T 细胞共孵育,然后进行流式细胞术和细胞因子分析,我们定量测定了抗 HER2 CAR-T 细胞的抗原特异性和剂量依赖性激活。我们还证明,aaTP 可以作为一种清洁的靶细胞,用于证明下一代 CAR-T 产品的作用机制的研究。总的来说,aaTP 的简单、廉价、模块化和精确可控的合成特性使得开发清洁和标准化的 CAR-T 细胞检测方法成为可能,与传统使用靶细胞系的检测方法相比具有重要优势。aaTP 的设计可以扩展到包括其他肿瘤抗原和生理靶细胞的相关表面分子。因此,aaTP 平台具有成为常规和新型 CAR-T 产品开发和评估的标准化工具的巨大潜力,特别是在获得监管机构批准和临床转化方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d834/9632174/38f4679262c3/fimmu-13-994532-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验