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CELL EXPANSION BIOREACTORS FOR ASSAY-READY IMMUNOCOMPETENT PATIENT MODELS

用于检测准备的免疫功能正常患者模型的细胞扩增生物反应器

基本信息

批准号：
10688981
负责人：
Kacey Ronaldson
金额：
$ 32.78万
依托单位：
LINK BIOSYSTEMS INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10688981
关键词：
3-Dimensional Address Animals Apoptosis Autologous Benchmarking Biological Biological Assay Biological Products Bioreactors Cause of Death Cell Count Cell Culture Techniques Cell Proliferation Cells Characteristics Clinical Companions Consumption Custom Development Devices Drug Combinations Drug Screening Drug resistance Feedback Gases Genetic Drift Goals Growth Heterogeneity Hospitals Human Immune Immunocompetent Immunologics Immunotherapy In Vitro Institution Link Maintenance Malignant Neoplasms Methodology Methods Modeling Molecular Profiling Morphology Mus Nutrient Oncology Organoids Outcome Output Paracrine Communication Pathologist Patient-Focused Outcomes Patients Performance Perfusion Pharmaceutical Preparations Phase Phenotype Plague Preclinical Drug Development Preparation Process Regimen Reproducibility Research Personnel Resistance Sampling Sensitivity and Specificity Serum-Free Culture Media Small Business Innovation Research Grant Technology Therapeutic Time Tissues Translating Variant Work biobank cancer subtypes cost cost efficient design drug sensitivity head-to-head comparison immunomodulatory therapies improved manufacturing process neoplastic cell novel therapeutics optimal treatments parallel processing patient derived xenograft model patient population patient response patient screening patient subsets pre-clinical precision drugs precision medicine predict clinical outcome predictive modeling preservation prototype rare cancer response screening shear stress single-cell RNA sequencing success timeline tool tumor user-friendly

项目摘要

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.

项目总结/摘要虽然癌症是全球死亡的主要原因，但肿瘤药物的成功率最低，成本最高，大多数是为了发展，并不断在动物身上显示出有希望的结果，然后在病人身上失败。因此需要一种模型来帮助理解药物如何在人体和特定患者中起作用人口。人类肿瘤样本的可用性将进一步促进增强的临床前筛选，时间长（>10年）、成本高（26亿美元）和成功率低（1/5，000）困扰着新技术的开发。毒品Link Biosystems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其使用确定的无血清培养基并依赖于受控的聚集以增强旁分泌信号传导，细胞-细胞接触，通过低剪切灌注增强营养输送，以及器官型组织小生境，数千个相同的免疫活性类肿瘤组织，可以根据需要进一步缩放。这种方法将能够建立早期和晚期癌症、罕见癌症和先前生物库样本的数量适合筛选大型药物组-包括免疫疗法，生物制剂和药物-药物组合，以找到最佳有效的药物方案，具体病人。此外，大规模产生质量受控的患者细胞的能力将使其能够用于治疗癌症。建立患者肿瘤生物库和随后的个性化药物筛选，以获得最佳治疗指导和克服耐药表型。为此，我们正在评估我们的生物反应器，用于扩展直接患者肿瘤样品和先前生物库的类器官模型的多用途，提供下游药物筛选测定所需的原材料，所述测定是人的、稳健的、可再现的，结合了免疫和基质成分，并捕获了患者反应的异质性。