大规模生产肿瘤免疫治疗合成细菌囊泡分离方法的优化

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Negar Ordouzadeh, Rossella Crescitelli, Agnes Zimmer, Petra Tjärnlund, Cecilia Lässer, Jan Lötvall, Kyong-Su Park
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引用次数: 0

摘要

细菌囊泡已成为治疗包括癌症在内的多种疾病的候选治疗药物。然而,考虑到诱导全身性炎症,其安全性仍然值得关注。为了解决这个问题,半合成细菌囊泡(SyBV)最近被开发出来,直接从细菌细胞膜中提取。这些囊泡毒性降低,但保留了免疫调节能力,这对免疫肿瘤学的目的是重要的。本研究对SyBV的生产工艺进行了进一步的细化,以达到良好生产规范(GMP)的标准。优化方法重新考虑了多个步骤,包括离心步骤的调整、苯并酶处理和消除超声步骤,从而产生了一套新的优化SyBV,命名为SyBVOpti。与使用先前方案分离的SyBV类似,SyBVOpti不激活巨噬细胞,但以剂量依赖的方式刺激树突状细胞产生IL-12 -此外,这些囊泡在恶性黑色素瘤模型中减弱肿瘤生长。此外,优化的工艺适用于GMP兼容的大肠杆菌源,在GMP条件下生产SyBVOpti。总的来说,这些发现描述了一种可靠的大规模生产SyBV的技术,并保留了治疗潜力,允许GMP生产和将这些生物活性囊泡转化为临床实践。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Optimization of the Isolation Method for Large-Scale Production of Synthetic Bacterial Vesicles for Cancer Immunotherapy

Optimization of the Isolation Method for Large-Scale Production of Synthetic Bacterial Vesicles for Cancer Immunotherapy

Optimization of the Isolation Method for Large-Scale Production of Synthetic Bacterial Vesicles for Cancer Immunotherapy

Optimization of the Isolation Method for Large-Scale Production of Synthetic Bacterial Vesicles for Cancer Immunotherapy

Optimization of the Isolation Method for Large-Scale Production of Synthetic Bacterial Vesicles for Cancer Immunotherapy

Bacterial vesicles have emerged as therapeutic drug candidates to treat a wide range of diseases, including cancer. However, critical concerns remain regarding their safety, in view of inducing systemic inflammation. To address this, semi-synthetic bacterial vesicles (SyBV) have recently been developed, directly derived from bacterial cell membranes. These vesicles have reduced toxicity but retained immunomodulatory ability, which is important for immuno-oncology purposes. In this study, the manufacturing process of SyBV has been further refined to meet Good Manufacturing Practice (GMP) standards. Multiple steps are reconsidered in the optimized method, including adaptation of centrifugation steps, benzonase treatment, and elimination of sonication steps, thereby producing a new set of optimized SyBV, designated as SyBVOpti. Similarly to SyBV isolated using the previous protocol, SyBVOpti do not activate macrophages but stimulate dendritic cells to produce IL-12 in a dose-dependent manner—moreover, these vesicles attenuate tumor growth in vivo in a model of malignant melanoma. Further, the optimized process applies to a GMP-compatible Escherichia coli source for producing SyBVOpti under GMP conditions. Collectively, these findings describe a reliable technique for large-scale production of SyBV with preserved therapeutic potential, allowing GMP manufacturing and translation of these bioactive vesicles into clinical practice.

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来源期刊
Advanced Therapeutics
Advanced Therapeutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.10
自引率
2.20%
发文量
130
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