Acute lymphocytic leukemia (ALL) is a common childhood cancer in the United States, with over 6000 new cases diagnosed each year. Administration of bacterial asparaginase (ASNase) has improved survival rates to nearly 80%, however these therapeutics have high incidence of immunological neutralization and serum activity must be monitored for most effective treatment regimens. Here, a 72% improvement in cell-free protein synthesis (CFPS) of FDA approved l-asparaginase (crisantaspase) is demonstrated by employing an aspartate-fed-batch reactor format. A CFPS-based ASNase activity assay as a tool for therapeutic regimentation and production quality control is also presented. This work suggests that shelf-stable and low-cost Escherichia coli-based CFPS reactions may be employed on-demand to 1) synthesize biologics on-site for patient administration, 2) verify biologic activity for dosage calculations, and 3) monitor therapeutic activity in human serum during the treatment regimen. The combination of both therapeutic production and activity assessment introduces a concept of synergistic utility for bacterial cell lysates in modern medical treatment. Indeed, recent work with CFPS biosensors supports a not-too-distant future when shelf-stable E. coli CFPS systems are used to diagnose, treat, and monitor treatment of diseases in the clinical setting.

中文翻译：

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工程性无细胞蛋白质合成，用于高产和天冬酰胺酶的人体血清活性评估：急性淋巴细胞白血病的按需治疗。

急性淋巴细胞白血病（ALL）是美国常见的儿童期癌症，每年诊断出6000多例新病例。施用细菌天冬酰胺酶（ASNase）可使存活率提高到近80％，但是这些治疗剂具有很高的免疫中和率，必须针对最有效的治疗方案监测血清活性。在此，通过采用天冬氨酸分批补料的反应器形式，证明了FDA批准的I-天冬酰胺酶（crisantaspase）的无细胞蛋白质合成（CFPS）改善了72％。还介绍了基于CFPS的ASNase活性测定法，作为治疗方法和生产质量控制的工具。这项工作表明，可以按需使用稳定的低成本低成本基于CFPS的CFPS反应，以进行以下操作：1）在现场合成生物制剂以进行患者给药，2）验证生物活性以进行剂量计算，以及3）在治疗方案中监测人血清中的治疗活性。治疗性生产和活性评估的结合引入了现代医学中细菌细胞裂解物协同效用的概念。的确，当在临床环境中使用货架稳定的大肠杆菌CFPS系统来诊断，治疗和监测疾病的治疗时，与CFPS生物传感器的最新工作支持的前景并不遥远。