Capture and Characterization of Highly Metastatic Cancer Cell Clusters in Transit from Lung Cancer Patient Whole Blood Specimens.

从肺癌患者全血样本中捕获和表征运输中的高度转移性癌细胞簇。

• 批准号: 10255872
• 负责人: Jeffrey Keith Allen
• 金额: $ 39.3万
• 依托单位: TUMORGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10255872
• 关键词: Aftercare; Antibodies; Autologous; Biological Assay; Biomimetics; Blood; Blood Circulation; Blood Vessels; Blood specimen; Cancer Cluster; Cancer Etiology; Cancer Patient; Cells; Cessation of life; Client; Clinical; Collection; Cytokeratin; Data; Detection; Development; Disseminated Malignant Neoplasm; Distant; Distant Metastasis; Drug Targeting; Epidermal Growth Factor Receptor; Exhibits; Fibroblasts; Genetic; Genomic approach; Genomics; Goals; Guidelines; Histologic; Human; Hyaluronic Acid; Immunohistochemistry; Immunologic Surveillance; Immunotherapy; Individual; Lead; Legal patent; Link; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Metastatic to; Methods; Microfluidic Microchips; Microfluidics; National Comprehensive Cancer Network; Neoplasm Metastasis; Non-Malignant; Oncology; Organ; Outcome; Patient-Focused Outcomes; Patients; Performance; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Phenotype; Primary Neoplasm; Process; Proliferating; Proteins; Recurrence; Sampling; Stains; Stream; Stromal Cells; System; Technology; Therapeutic; Time; Validation; Whole Blood; base; cancer cell; cancer therapy; cell type; circulating cancer cell; density; drug candidate; drug discovery; innovation; innovative technologies; interest; lung cancer cell; lung cancer screening; metastatic process; mortality; new technology; new therapeutic target; novel; novel therapeutics; pre-clinical research; prevent; prospective; rare cancer; targeted treatment; technology validation; tool; transcriptome sequencing; tumor microenvironment; tumorigenic; validation studies; vector; virtual

Project Summary Great progress has been made in treating cancer, however metastasis for most patients remains incurable, causing up to 90% of cancer deaths. Metastasis accounts for 8 million deaths per year worldwide and very few therapeutic options are available that prevent the spread of cancer. The metastatic process often begins with clusters of cancer cells that leave the primary tumor and enter circulation in the blood stream. Upon dissemination into distant organs, these clusters survive and give rise to proliferating metastatic tumors, which in turn can lead to additional metastases. While virtually all oncology-related drugs aim to kill cancer cells within a primary tumor, no drugs are available to target metastatic cell clusters in transit. As a consequence, it is nearly impossible to block or prevent the metastatic cascade. However, it has been recently shown that targeting these circulating highly metastatic cancer cell clusters can significantly reduce the spread of cancer. This discovery strengthens the urgent need to identify unique drug targets specific to these clusters. We recently developed and produced a microfluidic device that allows the specific capture and characterization of these cancer cell clusters from a patient’s blood sample. Integrated into our technology, we utilize a completely novel dual-capture approach based on a combination of biomimicry and immuno-capture. This dual-capture approach provides a substantial advantage since it biases capturing the most malignant cancer cell clusters. This exciting new technology will enable the focused characterization of these clusters and allow the development of a new class of anti-metastatic therapies, the ‘Cluster-Busters’, that will delay or prevent metastasis in cancer patients. Thus, within this technology validation application, we aim to screen lung cancer patients’ blood samples for circulating cancer cell clusters using our novel capture approach. A substantial advantage imparted by our approach is the collection of viable and naïve clusters allowing phenotypic, genomic, and functional assays. We will characterize these clusters using established tools, such as immunohistochemistry and RNA-sequencing. The conclusion of our study will confirm our technology’s ability to expedite the discovery of novel drug targets.

项目摘要 癌症的治疗已经取得了很大的进展，但大多数患者的转移仍然无法治愈， 导致高达90%的癌症死亡。转移每年造成全球800万人死亡， 有预防癌症扩散的治疗选择。转移过程通常始于 离开原发肿瘤并进入血流循环的癌细胞簇。传播后 当这些肿瘤转移到远处的器官时，这些集群存活下来并产生增殖的转移性肿瘤，这反过来又会导致 转移到其他地方虽然几乎所有的肿瘤相关药物都旨在杀死原发性肿瘤中的癌细胞， 没有药物可用于靶向转运中的转移性细胞簇。因此，几乎不可能 阻断或阻止转移级联反应。然而，最近的研究表明， 高转移性癌细胞簇可显著减少癌症的扩散。这一发现加强了 迫切需要确定针对这些集群的独特药物靶点。 我们最近开发并生产了一种微流控装置， 这些癌细胞簇的样本。结合我们的技术，我们完全利用 基于仿生和免疫捕获的组合的新型双捕获方法。这种双重捕获 这种方法提供了实质性的优势，因为它偏向于捕获最恶性的癌细胞簇。 这项令人兴奋的新技术将使这些集群的集中表征，并允许 开发一种新的抗转移疗法，即“肿瘤克星”， 癌症患者的转移。 因此，在这项技术验证应用中，我们的目标是筛选肺癌患者的血液样本， 循环癌细胞集群使用我们的新的捕获方法。这是我们的一个巨大优势， 方法是收集可行的和幼稚的集群，允许表型，基因组和功能测定。我们 将使用已建立的工具，如免疫组织化学和RNA测序来表征这些簇。 我们的研究结论将证实我们的技术有能力加快发现新的药物靶点。