Diagnostic Assays for OVCA Recurrence using Paraneoplastic Antigens and Epitopes

使用副肿瘤抗原和表位诊断 OVCA 复发

• 批准号: 8753213
• 负责人: MICHAEL A TAINSKY
• 金额: $ 16.53万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-07 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8753213
• 关键词: Affect; Amino Acids; Antigen Targeting; Antigens; Appearance; Autoantibodies; Autoantigens; Autoimmune Diseases; Binding; Biological Assay; Biological Markers; CA-125 Antigen; Cancer Patient; Clinical; Clinical Management; Cloning; Detection; Development; Diagnosis; Diagnostic; Disease; Enzyme-Linked Immunosorbent Assay; Epitopes; European Organization for Research and Treatment of Cancer; Goals; Homologous Gene; Homologous Protein; Immunoassay; Immunoglobulins; Laboratories; Length; Ligase; Malignant Neoplasms; Malignant neoplasm of ovary; Methods; Myositis; Neurologic; Neurons; Ovarian Carcinoma; Ovarian Serous Adenocarcinoma; Paraneoplastic Syndromes; Patients; Phage Display; Platinum; Polymyositis; Prior Chemotherapy; Proteins; RNA; Recombinant Proteins; Recurrence; Relapse; Sampling; Screening for Ovarian Cancer; Sensitivity and Specificity; Serologic tests; Serum; Serum Proteins; Staging; Symptoms; Testing; Therapeutic Intervention; Time; Woman; antigen binding; base; cancer recurrence; chemotherapy; cohort; expectation; follow-up; improved; lung small cell carcinoma; muscular system; prospective; public health relevance; tumor; validation studies

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.

描述（由申请方提供）：复发性卵巢癌（OVCA）的管理是一项重大的临床挑战，因为基于铂类的一线化疗后复发目前没有除CA 125之外的临床实验室生物标志物，CA 125具有局限性。最近的一项MRC/EORTC试验表明，CA 125升高的OVCA患者在出现复发的临床症状之前接受化疗的治疗，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，它们与血清自身抗体生物标志物结合，可以在CA 125之前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性自身抗原同源，副肿瘤性自身抗原是由隐性肿瘤产生的蛋白质，隐性肿瘤导致起源为自身免疫的神经系统或肌炎疾病。副肿瘤综合征患者随后从这些隐匿性肿瘤发展出癌症的临床体征。我们将进一步研究这些血清自身抗体生物标志物，以1）我们克隆的自身抗原和2）同源全长副肿瘤抗原蛋白，使用来自诊断为III/IV期铂敏感性浆液性卵巢腺癌的女性的前瞻性随访血清。我们希望这个新的队列证明这种多分析物检测在CA 125之前检测复发性OVCA的有用性。这将是一项探索性研究，旨在开发一种可在任何临床血清学实验室进行的多自身抗体检测（如ELISA样分析），从而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的检测将提高总生存率，因为它将比目前的方法更早地检测到肿瘤的再生长。我们的目标是确定最有用和准确的表位或副肿瘤蛋白，并开发这些诊断检测方法，使它们可以用于复发性卵巢癌的更有效的治疗干预。