MAF

ORLANDO, Fla., April 18, 2023 /PRNewswire/ -- DELFI Diagnostics, Inc., a pioneering developer of a new class of high-performance, accessible liquid biopsy tests for early cancer detection and monitoring, presented proof-of-concept data demonstrating how DELFI's platform can be used for monitoring the treatment of patients with advanced cancer without requiring any prior genomic information about the patient's tumor. The data were presented at the American Association for Cancer Research (AACR) 2023 Annual Meeting and builds on earlier studies showing the potential of using DELFI's technology for treatment monitoring. The DELFI-Tumor Fraction (DELFI-TF) score tracked mutant-allele fraction scores (MAFs) in side-by-side assessments, and also identified cancer signals in patients with clinical disease burden who had false negative MAF assays. Today, MAF assays are a common clinical measure of tumor burden. Researchers demonstrated that the DELFI-TF score and MAF results were equally predictive of clinical outcomes, and that changes in DELFI-TF scores over time anticipated later changes in radiologic assessments of disease response. "Legacy liquid biopsy approaches to cancer treatment monitoring rely either on prior knowledge about the genomic makeup of a patient's tumor or deep sequencing looking for expected alterations. Each approach is high cost, and subject to various types of errors and failures," said Peter Bach, MD, DELFI's Chief Medical Officer. "These proof of concept findings show that the whole-genome fragmentation analysis that underlies the DELFI-TF assay could be used to measure tumor burden, patient prognosis, and treatment response without the need for tumor tissue." Researchers from DELFI and the Netherlands Cancer Institute, and the University Medical Center Utrecht looked at 174 patients undergoing therapy for metastatic colorectal cancer and collected a total of 692 blood samples at various time points before and after treatment. They found that the DELFI-TF score predicted survival outcomes in the overall study population, regardless of the patient's BRAF or RAS status, two genes that are commonly mutated in CRC. Patients whose change in DELFI-TF was below the median over time showed both longer progression-free survival (HR = 2.03, 95% CI: 1.247-3.318) and overall survival (HR = 3.05, 95% CI: 1.58 - 5.90). The study builds on prior work demonstrating the potential of the DELFI platform to monitor patients with metastatic cancer undergoing treatment with immunotherapy. In that study, presented at ESMO in 2022, researchers showed that the DELFI-TF score was as effective as imaging at tracking progression and progression-free survival. The work was awarded "Best Poster" in the Translational Research, Tumor Agnostic session. "This is another example of the power of DELFI's unique platform to provide high quality results using low-cost methods and a common wet-lab process that is used in all our applications and products in development," said Nicholos Dracopoli, PhD, DELFI Co-Founder and Chief Scientific Officer. Also at AACR, DELFI and other researchers using the DELFI platform presented data describing the platform's strong performance in a training set that will be used to develop DELFI's first lung cancer screening product. Researchers also shared promising initial data on the DELFI platform's ability to detect early stage ovarian cancer. About DELFI Diagnostics DELFI Diagnostics is developing a new class of liquid biopsy tests for early cancer detection based on altered genome-wide fragmentation pro also known as "fragmentomes," representing aberrant packaging of DNA in cancer cells. By applying advanced machine learning algorithms, these fragment patterns are detectable at a very low sequencing cost. DELFI ("DNA EvaLuation of Fragments for early Interception") is using this technology to develop highly sensitive and specific cancer detection assays intended for wide and cost-effective distribution and adoption globally.

来自中国科学技术大学等机构的科学家们通过研究揭示了肝脏中驻留的巨噬细胞库普弗细胞所介导的机体免疫监视的新机制，该机制或有望预防肝脏转移的发生。 肝脏转移是最常见的恶性疾病之一，目前尚无有效的治疗手段，作为最大的肝脏巨噬细胞群体，对库普弗细胞（KCs，Kupffer cells）的功能性重编程或有望帮助治疗肝癌，但目前仍很少被采用。近日，一篇发表在国际杂志Journal of Clinical Investigation上题为“In situ expansion and reprogramming of Kupffer cells elicits potent tumoricidal immunity against liver metastasis”的研究报告中，来自中国科学技术大学等机构的科学家们通过研究揭示了肝脏中驻留的巨噬细胞库普弗细胞所介导的机体免疫监视的新机制，该机制或有望预防肝脏转移的发生；此外，研究人员还开发了一种原位靶向性表达和对库普弗细胞的抗肿瘤功能重塑的新方法，其或能成功清除各种终末期肝脏转移的癌症动物模型机体中的肿瘤，从而就能提供一种新方法来帮助开发治疗转移性肝癌的临床免疫疗法。 有超过90%的癌症患者都死于肿瘤转移，其中癌症肝脏转移最常见，且患者预后较差；目前，治疗肝脏转移的临床疗法选择非常有限，且与肝脏的免疫耐受有关，基于T细胞的免疫疗法策略往往也不能让患者得到最佳的反应，因此，研究人员就非常有必要开发出更为有效的免疫疗法策略了。 中国科学家开发出新型靶向性疗法来治疗癌症肝脏转移。 图片来源：Journal of Clinical Investigation (2023). DOI:10.1172/JCI157937 肝脏中含有更多名为库普弗细胞的组织巨噬细胞，其因强大的吞噬功能和较快的免疫反应，从而在肝脏的天然免疫监视作用中扮演着重要的角色；如今研究人员已经阐明，库普弗细胞在肝脏转移过程中早期的肿瘤抑制上扮演着必要的角色，然而，在肝脏转移的晚期阶段其功能就会被损伤，此外，结合临床样本和动物模型，研究人员发现，肝脏转移会逐渐诱导肿瘤周围的库普弗细胞发生选择性地丧失，并能阻止其进入肿瘤且发挥着一定的抗肿瘤效应。 基于这一研究发现，研究人员开发了一种携带CRISPR-CasΦ元件的低毒性工程化大肠杆菌，其能特异性靶向作用库普弗细胞并对其进行原位基因编辑，靶向失活库普弗细胞中能调节巨噬细胞增殖和功能的两个关键转录因子（c-Maf和MafB）就能诱导肿瘤相关的库普弗细胞进行快速扩张，且能促进促炎性功能性改变，明显增强肿瘤中库普弗细胞的浸润以及其吞噬肿瘤细胞的能力，从而就能重塑肿瘤的免疫微环境并诱导长期有效的抗肿瘤T细胞反应。 这一新型策略或能成功清除多种癌症肝脏转移的末期小鼠模型机体的肿瘤，包括黑色素瘤、结肠癌和肺癌等；相关研究结果表明，这种免疫疗法或能用于解决肝脏转移的问题，并强调了将针对组织中驻留的巨噬细胞的定向疗法作为一种新型抗癌疗法。综上，本文研究结果表明，研究人员开发的新型免疫疗法策略或能用于治疗癌症肝脏转移，同时还提出了靶向作用癌症中组织驻留的巨噬细胞的治疗潜力。（生物谷Bioon.com） 原始出处： Wei Liu,Xia Zhou,Qi Yao, et al. In situ expansion and reprogramming of Kupffer cells elicits potent tumoricidal immunity against liver metastasis, Journal of Clinical Investigation (2023). DOI: 10.1172/JCI157937

肝脏转移是最常见的恶性疾病之一，目前尚无有效的治疗手段，作为最大的肝脏巨噬细胞群体，对库普弗细胞（KCs，Kupffer cells）的功能性重编程或有望帮助治疗肝癌，但目前仍很少被采用。近日，一篇发表在国际杂志Journal of Clinical Investigation上题为“In situ expansion and reprogramming of Kupffer cells elicits potent tumoricidal immunity against liver metastasis”的研究报告中，来自中国科学技术大学生命科学与医学部曾筑天课题组通过研究揭示了肝脏中驻留的巨噬细胞库普弗细胞所介导的机体免疫监视的新机制，该机制或有望预防肝脏转移的发生；此外，研究人员还开发了一种原位靶向性表达和对库普弗细胞的抗肿瘤功能重塑的新方法，其或能成功清除各种终末期肝脏转移的癌症动物模型机体中的肿瘤，从而就能提供一种新方法来帮助开发治疗转移性肝癌的临床免疫疗法。有超过90%的癌症患者都死于肿瘤转移，其中癌症肝脏转移最常见，且患者预后较差；目前，治疗肝脏转移的临床疗法选择非常有限，且与肝脏的免疫耐受有关，基于T细胞的免疫疗法策略往往也不能让患者得到最佳的反应，因此，研究人员就非常有必要开发出更为有效的免疫疗法策略了。中国科学家开发出新型靶向性疗法来治疗癌症肝脏转移。图片来源：Journal of Clinical Investigation (2023). DOI:10.1172/JCI157937肝脏中含有更多名为库普弗细胞的组织巨噬细胞，其因强大的吞噬功能和较快的免疫反应，从而在肝脏的天然免疫监视作用中扮演着重要的角色；如今研究人员已经阐明，库普弗细胞在肝脏转移过程中早期的肿瘤抑制上扮演着必要的角色，然而，在肝脏转移的晚期阶段其功能就会被损伤，此外，结合临床样本和动物模型，研究人员发现，肝脏转移会逐渐诱导肿瘤周围的库普弗细胞发生选择性地丧失，并能阻止其进入肿瘤且发挥着一定的抗肿瘤效应。基于这一研究发现，研究人员开发了一种携带CRISPR-CasΦ元件的低毒性工程化大肠杆菌，其能特异性靶向作用库普弗细胞并对其进行原位基因编辑，靶向失活库普弗细胞中能调节巨噬细胞增殖和功能的两个关键转录因子（c-Maf和MafB）就能诱导肿瘤相关的库普弗细胞进行快速扩张，且能促进促炎性功能性改变，明显增强肿瘤中库普弗细胞的浸润以及其吞噬肿瘤细胞的能力，从而就能重塑肿瘤的免疫微环境并诱导长期有效的抗肿瘤T细胞反应。这一新型策略或能成功清除多种癌症肝脏转移的末期小鼠模型机体的肿瘤，包括黑色素瘤、结肠癌和肺癌等；相关研究结果表明，这种免疫疗法或能用于解决肝脏转移的问题，并强调了将针对组织中驻留的巨噬细胞的定向疗法作为一种新型抗癌疗法。综上，本文研究结果表明，研究人员开发的新型免疫疗法策略或能用于治疗癌症肝脏转移，同时还提出了靶向作用癌症中组织驻留的巨噬细胞的治疗潜力。原始出处：Wei Liu,Xia Zhou,Qi Yao, et al. In situ expansion and reprogramming of Kupffer cells elicits potent tumoricidal immunity against liver metastasis, Journal of Clinical Investigation (2023). DOI: 10.1172/JCI157937