Biomarker Investigations for Clinical Trials

与上述特定的生物标记物目标相关，我们进行了各种研究来支持生物标记物驱动的早期药物开发：1.新的或新的生物标记物在高度独特的治疗药物的早期试验中的应用。A)我们支持Raffit Hassan博士使用我们之前开发的分析方法(JCO Precis Onol)对他的以间硫蛋白为靶标的新疗法进行的相关标记研究，包括传统的抗体药物结合疗法和T细胞疗法。DOI：10.1200/PO.17.00282,2018年)。在许多患者中看到了显著的反应，我们的肿瘤抗原测试几乎是实时进行的，以向研究人员提供有关反应和进展的及时信息。根据我们设施的新重点，该项目从我们这边完成，化验能力转移到哈桑博士的实验室。B)我们为Andrea Apolo博士的临床试验提供持续的生物标记物支持，并发表了一些工作(Girardi DM，临床癌症研究，DOI：10.1158/1078-0432)。2022年)。该项目已完成，并已终止。C)我们建立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、癌症基因分型和患者选择。我们支持Scott Norberg博士进行的HPV靶向治疗试验。最近的一些工作集中在利用NGS和游离DNA来对抗T细胞疗法的耐药机制。此外，这一项目也已完成并终止。D)对染色体检测结果异常的孕妇进行游离DNA体细胞突变分析。在与NICHD的Christina Annunziata和Diana Bianci博士合作中，我们进行了一些开创性的工作，以揭示肿瘤特异性体细胞突变，为癌症的起源、常见的致病过程和治疗药物选择提供信息。中期结果展示了该领域的一些有意义的新知识，这些知识可能会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。我们专注于开发一种基于循环肿瘤DNA的技术，用于预测孕妇癌症的发展，并确定与癌症相关的癌症基因突变。我们目前正在研究一种无细胞DNA测试，用于研究在NICHD的Diana Bianci博士领导的一项试验中出现异常NIPT测试结果的孕妇的潜在肿瘤。

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.