Biomarker Investigations for Clinical Trials

与上述特定的生物标志物目标相关，我们进行了各种研究来支持生物标志物驱动的早期药物开发：在高度独特的治疗药物的早期试验中应用新的或新颖的生物标志物。A)我们支持Raffit Hassan博士的间皮素靶向新疗法的相关标记研究，包括传统的抗体药物偶联疗法和T细胞疗法，使用我们之前开发的检测方法（JCO Precis Oncol）。doi: 10.1200/PO.17.00282, 2018)。在许多患者中发现了显著的反应，我们的肿瘤抗原检测几乎实时进行，为研究人员提供了有关反应和进展的及时信息。根据我们设施的新重点，我们这边完成了这个项目，化验能力转移到了哈桑博士的实验室。B)我们为Andrea Apolo博士的临床试验提供了持续的生物标志物支持，并发表了部分工作（Girardi DM, clinycancer Res, doi: 10.1158/1078-0432）。2022)。本项目已完成并终止。C)我们开发了一种宫颈癌的无细胞DNA检测方法，并将其用于治疗监测、最小残留病（MRD）检测、癌症基因分型以供患者选择。我们支持斯科特·诺伯格博士的hpv靶向治疗试验。最近的一些工作集中在使用NGS与细胞游离DNA对抗T细胞治疗的抗性机制。此外，该项目已完成并终止。D)染色体检测结果异常孕妇的体细胞突变与游离DNA分析。在与NICHD的Christina Annunziata和Diana Bianchi博士的合作中，我们进行了一些开创性的工作，揭示了肿瘤特异性的体细胞突变，为癌症的起源、常见的致病过程和治疗药物的选择提供了信息。中期结果提供了一些重要的新知识，这些知识可能影响患者的临床管理，并为利用染色体非整倍体进行癌症筛查的可行性提供信息。我们专注于基于循环肿瘤DNA技术的发展，以预测孕妇癌症的发展，并确定与癌症相关的癌症基因突变。目前，在NICHD的Diana Bianchi博士的带领下，我们正在进行一项无细胞DNA测试，用于调查NIPT测试结果异常的孕妇的潜在肿瘤。

Related to the specific biomarker goals above, we conducted various studies to support biomarker driven early-stage drug development: 1. Application of new or novel biomarkers in early-stage trials of highly unique therapeutic agents. A) We supported correlative marker investigations of Dr. Raffit Hassan on his mesothelin-targeted novel therapies, including traditional antibody drug conjugate therapies, and T cell therapies, using the assay that we have previously developed (JCO Precis Oncol. doi: 10.1200/PO.17.00282, 2018). Significant responses were seen in many patients, where our tumor antigen tests were performed in near real time to provide investigators with timely information on responses and on progression. According to the new focus of our facility, the project was completed from our side and assay capabilities were transferred to Dr. Hassan's lab. B) We provided continues biomarker support of clinical trials by Dr. Andrea Apolo and some of the work was published (Girardi DM, Clin Cancer Res, doi: 10.1158/1078-0432. 2022). This project has been finalized and is terminated. C) We developed a cell free DNA detection for cervical cancer and use it for treatment monitoring, minimum residue disease (MRD) detection, cancer genotyping for patient selection. We support HPV-targeted therapy trials by Dr. Scott Norberg. Some of the recent work was focused on using NGS with cell free DNA for resistance mechanisms against T cell therapies. Also this project was completed and terminated. D) Somatic mutation analysis with cell free DNA in pregnant women with abnormal chromosome test results. In working with Christina Annunziata and Dr. Diana Bianchi of NICHD, we performed some pioneer work to uncover tumor specific somatic mutation informing on cancer origins, on common pathogenic processes, and on treatment drug options. Interim results presented some significant novel knowledge in the field which could impact the patient clinical management and inform on the feasibility of using chromosome aneuploidy for cancer screening. We focus on the development of a circulating tumor DNA based technology for predicting the development of cancer in pregnant women and for determining cancer gene mutations associated with cancer. We are currently working on a cell free DNA test for the investigation of potential neoplasia in pregnant women who presented with abnormal NIPT test results in a trial led by Dr. Diana Bianchi of NICHD.