IGF::OT::IGF SMALL BUSINESS INNOVATION RESEARCH PROGRAM (SBIR)

IGF::OT::IGF 小型企业创新研究计划 (SBIR)

• 批准号: 9162178
• 负责人: HAL CROSSWELL
• 金额: $ 22.5万
• 依托单位: KIYATEC, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2016-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9162178
• 关键词: Affect; Biological Assay; Biological Products; Biopsy; Biopsy Specimen; Bioreactors; Cancer Patient; Cancer cell line; Cell Line; Cell Separation; Cessation of life; Characteristics; Chemical Agents; Chemicals; Clinical; Coculture Techniques; Colony-Forming Units Assay; Communities; Curative Surgery; Elements; Epithelial; Ethnic Origin; Extracellular Matrix; Goals; Growth Factor; Human; In Vitro; Liquid substance; Malignant Neoplasms; Methods; Mission; Neoplasm Circulating Cells; Neoplasm Metastasis; Patients; Performance; Phase; Population; Primary Neoplasm; Process; Relapse; Research; Resistance; Small Business Innovation Research Grant; Stem cells; System; Techniques; Technology; Tissues; Tumor Debulking; Tumorigenicity; Undifferentiated; Whole Blood; Woman; Xenograft procedure; cancer cell; cancer stem cell; clinical application; drug development; drug testing; human tissue; in vivo; lung small cell carcinoma; men; next generation; novel; pre-clinical; programs; response; scaffold; stem cell population; stemness; therapeutic target; tumor; tumor microenvironment

The overall objective of this proposal is to develop an in vitro process by which cancer stem cells (CSC) can be isolated from primary human tumor biopsies or tissues, expanded without losing critical elements of stem cell qualities, and then used for preclinical and clinical applications. During this fast track proposal, KIYATEC will employ an integrated, functional and unbiased scientific strategy, in order to establish and standardize processes which are able to isolate and expand cancer stem cell populations derived from immortalized and patient‐derived xenograft cell lines and primary human tissues. Due to a combination of scientific and commercial factors, but driven by the large unmet clinical need in small cell lung cancer (SCLC), KIYATEC will focus on developing its CSC cultivation technology and methods on SCLC, a relatively rare and uniformly fatal cancer affecting men and women of all ethnicities. Debulking and curative surgeries that permit extra tissue for research are rarely performed, which has limited available tissue for cell lines and patient derived xenografts. There is, however, strong evidence that a tumor initiating or cancer stem cell populations exist in SCLC, both in primary tumors and in circulating tumor cells obtained from patient whole blood[1]. The ability to isolate and expand the rare CSC population from limited biopsy samples from patients and or the CTC population from “liquid biopsies” of patients would greatly aid the academic research community as well as biopharmaceutical companies who are increasingly focusing on rare tumor types with high unmet clinical need. By the end of phase I performance, KIYATEC will have identified the processes required to isolate and expand to greater than 10^7 functional and undifferentiated SCLC CSC from existing SCLC patient derived xenograft cell lines. By the end of phase II, KIYATEC will have confirmed the “stemness” of the expanded CSC derived from primary SCLC patient tissues, while developing and molecularly and functionally characterizing a SCLC PDX “bank” from at least 10 different SCLC patients. Importantly, this project is perfectly aligned with KIYATEC’s mission to provide direct and positive impact on patients with cancer, through accelerating the drug development of targeted therapeutics which will have the potential to eliminate the CSC population, the ultimate driver of metastasis, resistance, relapse and death due to cancer.

这样的总体目的是开发一种体外过程，可以从原发性人类肿瘤或组织中分离出癌症干细胞（CSC），而不会失去干细胞质量的批判性元素，而十个用于临床前和临床应用 由于科学和商业因素的结合，能够从永生和患者衍生的异种移植细胞系和RY人体组织中扩展癌症细胞种群的过程。 ，Kiyatec将重点放在SCLC EN和所有种族的妇女的培养技术上然而，有力的证据表明，在原发性肿瘤和从患者全血的循环肿瘤细胞中，肿瘤引发或癌症干细胞的人口占IST [1]患者和或来自患者的“流动活检”的人群应该是学术界，因为越来越多的临床需求的稀有肿瘤类型越来越重视稀有的肿瘤类型。分离并扩展到大于10^7的功能，并在II阶段结束时从现有的SCLC患者衍生的现有SCLC CSC延伸，确认源自原发性SCLC患者组织的CSC，同时发育和分子和分子功能从10个不同的SCLC患者中培养SCLC PDX“银行”。 CSC人口是转移，抗性，复发和死亡的最终驱动因素，原因是由于癌症。