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

该提案的总体目标是开发一种体外方法，通过该方法可以从原发性人类肿瘤活检或组织中分离癌症干细胞（CSC），在不损失干细胞质量的关键要素的情况下扩增，然后用于临床前和临床应用。在这一快速通道的建议，KIYATEC将采用综合，功能和公正的科学战略，以建立和标准化， 能够分离和扩增来源于永生化和患者来源的异种移植细胞系和原代人体组织的癌症干细胞群的方法。由于科学和商业因素的结合，但由于小细胞肺癌（SCLC）的大量未满足的临床需求，KIYATEC将专注于开发其CSC培养技术和SCLC方法，这是一种相对罕见且致命的癌症，影响所有种族的男性和女性。很少进行允许额外组织用于研究的减瘤和治疗性手术，这限制了用于细胞系和患者来源的异种移植物的可用组织。然而，有强有力的证据表明，肿瘤起始细胞或癌症干细胞群体存在于SCLC中，既存在于原发性肿瘤中，也存在于从患者全血中获得的循环肿瘤细胞中[1]。从患者的有限活检样本中分离和扩大罕见CSC人群和/或从患者的“液体活检”中分离和扩大CTC人群的能力将极大地帮助学术研究界以及越来越关注罕见肿瘤的生物制药公司。高度未满足的临床需求。在I期性能结束时，KIYATEC将确定从现有SCLC患者来源的异种移植细胞系中分离和扩增超过10^7个功能性和未分化SCLC CSC所需的工艺。到第二阶段结束时，KIYATEC将确认来自原发性SCLC患者组织的扩增CSC的“干性”，同时开发并从分子和功能上表征来自至少10名不同SCLC患者的SCLC PDX“库”。重要的是，该项目完全符合KIYATEC的使命，即通过加速靶向治疗药物的开发，为癌症患者提供直接和积极的影响，这将有可能消除CSC人群，这是癌症转移，耐药性，复发和死亡的最终驱动因素。

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.