CELL EXPANSION BIOREACTORS FOR ASSAY-READY IMMUNOCOMPETENT PATIENT MODELS

项目摘要/摘要 尽管癌症是全球主要的死亡原因，但肿瘤药物的成功率最低，成本最高 大多数是发展起来的，并在动物身上不断显示出有希望的结果，然后在患者身上失败。因此，在那里 是需要有助于理解药物如何在人类和特定患者身上发挥作用的模型 人口。人类肿瘤样本的获得将进一步促进增强的临床前筛查，其中 长时间(10年)、高成本(26亿美元)和低成功率(1/5,000)困扰着新产品的开发 毒品。Link BiosSystems通过定制的生物反应器产品提供了一种通用的肿瘤细胞扩增方法 它使用定义的无血清介质，并依靠受控聚集来增强旁分泌信号和 细胞-细胞接触，通过低剪切灌流增强营养输送，以及产生器官型组织生态位 数以千计相同的具有免疫功能的类瘤组织，可以根据需要进一步缩放。这种方法 将能够为早期和晚期癌症、罕见癌症以及 以前生物库样本的数量适合筛选大型药物小组--包括 免疫疗法、生物制品和药物-药物组合，以找到治疗该病的最佳有效药物方案 特定的病人。此外，大规模生产质量受控的患者细胞的能力将使 建立患者肿瘤生物库和随后的个性化药物筛选以实现最佳治疗 指导和克服耐药表型。为此，我们同样在评估我们的生物反应堆 用于扩展直接患者肿瘤样本和先前的生物库有机模型的多功能工具， 为下游药物筛选分析提供所需的原料，这些分析是人类的，坚固的，可重复性的， 结合了免疫和间质成分，并捕获了患者反应的异质性。

Project Summary/Abstract Although cancer is a leading cause of death globally, oncology drugs have the lowest success rates, cost the most to develop, and constantly show promising results in animals and then fail to work in patients. Thus, there is a need for models that facilitate understanding of how a drug will work in humans and for specific patient populations. The availability of human tumor samples will further facilitate enhanced preclinical screening, where long timelines (>10 years), high costs ($2.6B), and low success rates (1/5,000) plague the development of new drugs. Link Biosystems provides a universal approach to tumor cell expansion via a custom bioreactor product that uses a defined serum-free media and relies on controlled aggregation for enhanced paracrine signaling and cell-cell contact, enhanced nutrient delivery via low-shear perfusion, and organotypic tissue niches to generate thousands of identical immunocompetent tumoroid tissues that can be further scaled as needed. This approach would enable the establishment of robust tumor models for early and late stage cancers, rare cancers, and previously biobanked samples at quantities suitable for screening large drug panels – including immunotherapies, biologics, and drug-drug combinations, to find an optimally effective drug regimen for the specific patient. Additionally, the ability to generate quality-controlled patient cells at scale will enable the establishment of patient tumor biobanks and subsequent personalized drug screening for optimal treatment guidance and to overcome drug resistant phenotypes. To this end, we are similarly evaluating our bioreactors versatile utility for expansion of direct patient tumor samples and previously biobanked organoid models, providing the raw material needed for downstream drug screening assays that are human, robust, reproducible, incorporates immune and stromal components, and captures the heterogeneity of patient responses.