Oncolytic viruses are playing an increasingly important role in cancer immunotherapy applications. Given the preclinical and clinical efficacy of these virus-based therapeutics, there is a need for fast, simple, and inexpensive downstream processing methodologies to purify biologically active viral agents that meet the increasingly higher safety standards stipulated by regulatory authorities like the Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products. However, the production of virus materials for clinical dosing of oncolytic virotherapies is currently limited—in quantity, quality, and timeliness—by current purification technologies. Adsorption of virus particles to solid phases provides a convenient and practical choice for large-scale fractionation and recovery of viruses from cell and media contaminants. Indeed, chromatography has been deemed the most promising technology for large-scale purification of viruses for biomedical applications. The implementation of new chromatography media has improved process performance, but low yields and long processing times required to reach the desired purity are still limiting. Here we report the development of an interference chromatography-based process for purifying high titer, clinical grade oncolytic Newcastle disease virus using NatriFlo® HD-Q membrane technology. This novel approach to optimizing chromatographic performance utilizes differences in molecular bonding interactions to achieve high purity in a single ion exchange step. When used in conjunction with membrane chromatography, this high yield method based on interference chromatography has the potential to deliver efficient, scalable processes to enable viable production of oncolytic virotherapies.

中文翻译：

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干扰色谱法：一种优化色谱法选择性和分离性能以纯化病毒的新颖方法。

溶瘤病毒在癌症免疫治疗应用中起着越来越重要的作用。考虑到这些基于病毒的疗法的临床前和临床功效，需要一种快速，简单和廉价的下游加工方法来纯化具有生物活性的病毒制剂，这些制剂应满足食品药品监督管理局等监管部门规定的日益提高的安全标准。和欧洲药品评估机构。但是，目前的纯化技术在数量，质量和及时性方面限制了用于溶瘤病毒疗法临床给药的病毒材料的生产。病毒颗粒在固相上的吸附为大规模分离和从细胞和培养基污染物中回收病毒提供了方便实用的选择。实际上，色谱法已被认为是用于生物医学应用的病毒大规模纯化的最有前途的技术。新色谱介质的实施改善了工艺性能，但是达到所需纯度所需的低收率和较长的处理时间仍然受到限制。在这里，我们报告使用NatriFlo®HD-Q膜技术纯化基于高滴度的临床级溶瘤新城疫病毒的基于干扰色谱的方法的开发。这种优化色谱性能的新颖方法利用分子键合相互作用的差异，在单个离子交换步骤中获得高纯度。当与膜色谱法结合使用时，这种基于干扰色谱法的高收率方法有可能提供高效，可扩展的方法，以实现溶瘤病毒疗法的可行生产。