Diagnostic Assays for OVCA Recurrence using Paraneoplastic Antigens and Epitopes

描述（由申请人提供）：复发性卵巢癌（OVCA）的管理是一个主要的临床挑战，因为目前除了CA125有局限性外，铂类一线化疗后复发没有临床实验室生物标志物。最近的一项MRC/EORTC试验表明，在出现复发临床症状之前接受化疗的CA125升高的OVCA患者的治疗与在OVCA临床症状出现时开始治疗的患者相比，没有生存获益。需要新的OVCA复发生物标志物来提高总生存率。我们已经确定了一组三种抗原结合血清自身抗体生物标志物，可提前CA125 9个月检测复发性OVCA，平均灵敏度、特异性和准确性分别为94.7%、86.7%和93.3%。这些克隆的自身抗原与副肿瘤自身抗原同源，后者是由引起自身免疫性神经或肌炎疾病的隐匿肿瘤产生的蛋白质。副肿瘤综合征患者随后从这些隐匿的肿瘤发展为癌症的临床体征。我们将进一步研究这些血清自身抗体生物标志物，1)克隆的自身抗原和2)同源全长副肿瘤抗原蛋白，使用诊断为III/IV期卵巢铂敏感浆液性腺癌的妇女的前瞻性随访血清。我们希望这个新的队列能够证明这种多分析物检测在CA125之前检测复发性OVCA的有效性。这将是一项探索性研究，旨在开发一种多种自身抗体测试，如elisa样分析，可在任何临床血清学实验室进行，因此可以对复发性卵巢癌的症状前诊断产生直接影响。我们的期望是，这种复发性OVCA的测试将提高总体生存率，因为它将比目前的方法更早地检测到肿瘤的再生。我们的目标是确定最有用和最准确的表位或副肿瘤蛋白，并开发这些诊断检测方法，以便它们可以用于更有效的复发性卵巢癌治疗干预。

DESCRIPTION (provided by applicant): The management of recurrent ovarian cancer (OVCA) is a major clinical challenge because relapse after platinum-based front-line chemotherapy currently has no clinical laboratory biomarkers other than CA125 which has limitations. A recent MRC/EORTC trial demonstrated that treatment of OVCA patients with a rising CA125 who received chemotherapy prior to the appearance of clinical symptoms of recurrence had no survival benefit over those for whom therapy was initiated at the time of clinical symptoms of OVCA. New biomarkers of OVCA recurrence are needed to improve overall survival. We have identified a panel of three antigens that bind to serum autoantibody biomarkers that detect recurrent OVCA nine months in advance of CA125 with an average sensitivity, specificity, and accuracy of 94.7%, 86.7% and 93.3%, respectively. These cloned autoantigens are homologous to paraneoplastic autoantigens, proteins produced by occult tumors that cause neurological or myositis diseases that are autoimmune in origin. Paraneoplastic syndrome patients subsequently develop clinical signs of cancer from these occult tumors. We will further investigate these serum autoantibody biomarkers to 1) our cloned autoantigens and 2) homologous full length paraneoplastic antigenic proteins using sera from a prospective follow-up of women diagnosed with stage III/IV platinum-sensitive serous adenocarcinoma of the ovary. We expect this new cohort to demonstrate the usefulness of this multianalyte test to detect recurrent OVCA prior to CA125. This will be an exploratory study to develop a multi-autoantibody test such as an ELISA-like analysis that can be performed in any clinical serology lab and thus can make an immediate impact in presymptomatic diagnosis of recurrent ovarian cancer. Our expectation is that this test for recurrent OVCA will improve overall survival because it will detect the regrowth of tumors earlier than current methods. Our goal is to identify the most useful and accurate epitopes or paraneoplastic proteins and develop these diagnostic assays so that they can be used for more effective therapeutic interventions in recurrent ovarian cancer.