Biomarker Investigations for Clinical Trials

与上述特定生物标志物目标相关，我们进行了各种研究以支持生物标志物驱动的早期药物开发：新的或新型生物标志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哈桑博士关于其间皮素靶向的新疗法的相关标志物研究，包括传统的抗体药物缀合物疗法和T细胞疗法，使用我们先前开发的测定（JCO Precis Oncol. doi：10.1200/PO.17.00282，2018）。在许多患者中观察到显著的反应，其中我们的肿瘤抗原检测是在接近真实的时间内进行的，以向研究者提供关于反应和进展的及时信息。根据我们机构的新重点，我们完成了该项目，并将分析能力转移到哈桑博士的实验室。B）我们提供了Andrea Apolo博士的临床试验的持续生物标志物支持，并且一些工作已经发表（Girardi DM，Clin Cancer Res，doi：10.1158/1078-0432. 2022年）。该项目已经完成并终止。C）我们开发了宫颈癌的无细胞DNA检测，并将其用于治疗监测，最小残留疾病（MRD）检测，癌症基因分型以供患者选择。我们支持Scott Norberg博士的HPV靶向治疗试验。最近的一些工作集中在使用具有无细胞DNA的NGS用于针对T细胞疗法的抗性机制。该项目也已完成并终止。D）在具有异常染色体测试结果的孕妇中使用无细胞DNA进行体细胞突变分析。在与NICHD的Christina Annunziata和Diana比安奇博士的合作中，我们进行了一些开创性的工作，以发现肿瘤特异性体细胞突变，从而为癌症起源、常见致病过程和治疗药物选择提供信息。中期结果提出了该领域的一些重要的新知识，这些知识可能会影响患者的临床管理，并为使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检测，用于调查NIPT检测结果异常的孕妇的潜在肿瘤，该试验由NICHD的Diana比安奇博士领导。

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.