CapioCyte circulating tumor cell assay as a biomarker for cancer immunotherapy response

CapioCyte 循环肿瘤细胞测定作为癌症免疫治疗反应的生物标志物

• 批准号: 9988597
• 负责人: Steven Miller
• 金额: $ 0.2万
• 依托单位: CAPIO BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9988597
• 关键词: Address; Antibodies; Binding; Biological Markers; Biological Sciences; Biomimetics; Blood; Blood Tests; Blood specimen; Cancer Patient; Cell Adhesion Molecules; Cell Count; Cell Line; Cell Survival; Cells; Cellular Assay; Chemistry; Clinical; Clinical Data; Clinical Trials; Data; Dendrimers; Detection; Development; Devices; E-Selectin; Engineering; Epidermal Growth Factor Receptor; Epithelial Cells; Future; Generations; Genes; Goals; Gold; Hematopoietic Neoplasms; Human; Image; Immobilization; Immune system; Immunotherapy; Investigation; Kinetics; Lead; Licensing; Ligands; Malignant Neoplasms; Measures; Mediating; Methods; Monitor; Neoplasm Circulating Cells; Oncogenes; Oncogenic; Outcome; Patients; Pattern; Pharmacologic Substance; Phase; Proteins; Reagent; Reporting; Resistance; Sensitivity and Specificity; Series; Small Business Innovation Research Grant; Specificity; Stains; Surface; System; Technology; Testing; Time; Trademark; Translating; Treatment Cost; Validation; Work; base; cancer biomarkers; cancer cell; cancer immunotherapy; cancer therapy; clinical diagnostics; cohort; commercial application; commercialization; cost; cost effective; design; high throughput analysis; improved; innovation; liquid biopsy; neoplastic cell; novel; personalized cancer therapy; phase 1 study; predicting response; predictive marker; prototype; response; side effect; stem-like cell; success; transcriptome sequencing; treatment response

Cancer immunotherapy, the utilization of the patients’ own immune system to treat cancer, has emerged as a powerful new strategy in cancer treatment. An unmet need in cancer immunotherapy treatment has been the lack of a predictive biomarker for treatment response. Imaging, which has been the ‘gold standard” for monitoring treatment response is unreliable in immunotherapy due to the pseudoprogression phenomenon. An immunotherapy biomarker will enable more personalized cancer treatment, response-adaptive treatment and cost reduction. One potential approach for the development of such predictive biomarkers is to utilize circulating tumor cells (CTCs). However, the currently available systems such as CellSearch™ and other competing technologies do not have high enough sensitivity. Capio Biosciences has developed a novel biomimetic platform that is highly sensitive and specific in CTC capture. The tumor cell capture efficiency of the platform, which is trademarked as CapioCyte™, was shown to increase by up to 150-fold via a biomimetic combination of E-selectin-induced cell rolling and dendrimer-mediated multivalent binding. We have preliminary clinical data from various cohorts demonstrating that we can reliably capture high number of CTCs using CapioCyte™. To translate our technology, we aim to optimize our CapioCyte™ immunotherapy chip design. This proposed SBIR Phase I study will progress through 2 specific aims. In Aim 1, we will prepare and compare various CapioCyte™ capture surfaces with different combinations of capture agents to engineer an optimized chip using a series of cell lines. Surface chemistries will also be developed to achieve controlled immobilization of the capture agents and facile isolation of CTCs (detachment from the capture surfaces), enabling post-capture analyses. In Aim 2, the optimized CapioCyte™ prototype will be validated using human blood samples from cancer patients receiving immunotherapy. The sensitivity and specificity of the CapioCyte™ prototype will be measured and compared to those of CellSearch™. The captured CTCs will then be the subject of post-capture analysis, such as RNA sequencing, in addition to post-staining of the captured CTCs with aPD- L1 and p63. These efforts will reveal the relationship among kinetic changes of CTC counts, oncogene/target expression of CTCs, and clinical outcomes. Upon successful completion, we will have developed a biomarker for cancer immunotherapy response. Such a biomarker can ultimately enable personalized and response-adaptive immunotherapy cancer treatment.

癌症免疫疗法是患者自己的免疫系统治疗癌症的利用，已成为一种 癌症治疗中有力的新策略。癌症免疫疗法治疗的需求未满足的是 缺乏用于治疗反应的预测生物标志物。成像，这是监视的“黄金标准” 由于伪雌性现象，治疗反应在免疫疗法中是不可靠的。一个 免疫疗法生物标志物将实现更多个性化的癌症治疗，反应自适应治疗和 降低成本。开发这种预测性生物标志物的一种潜在方法是利用循环 肿瘤细胞（CTC）。但是，当前可用的系统（例如CelleChearch™和其他竞争） 技术没有足够高的灵敏度。 Capio Biosciences开发了一种新型的仿生型 在CTC捕获中高度敏感且具有特异性的平台。肿瘤细胞捕获的效率 平台被称为Capiocyte™，显示出通过仿生型增加150倍 电子选择蛋白诱导的细胞滚动和树突聚合物介导的多价结合的组合。我们有 来自各个队列的初步临床数据表明我们可以可靠地捕获大量CTC 使用Capiocyte™。为了翻译我们的技术，我们旨在优化Capiocyte™免疫疗法芯片 设计。这项拟议的SBIR I期研究将通过2个特定目标进行。在AIM 1中，我们将准备和 将各种Capiocyte™捕获表面与捕获剂的不同组合进行比较 使用一系列细胞系优化芯片。也将开发表面化学以实现受控的 固定捕获剂和CTC的容易隔离（与捕获表面脱离）， 启用捕获后分析。在AIM 2中，优化的Capiocyte™原型将使用人类进行验证 接受免疫疗法的癌症患者的血液样本。 Capiocyte™的灵敏度和特异性 原型将被测量并与CelleChearch™的原型进行比较。捕获的CTC将是主题 除了用APD-捕获的CTC染色后，捕获后分析（例如RNA测序） L1和P63。这些努力将揭示CTC计数，癌基因/目标的动力学变化之间的关系 CTC和临床结果的表达。成功完成后，我们将开发一个生物标志物 用于癌症免疫疗法反应。这样的生物标志物最终可以实现个性化和 反应 - 适应性免疫疗法癌症治疗。