Developing clinical, immunologic and radiographic tools to measure the clinical effect of immunotherapy in biochemically recurrent prostate cancer

 描述（由申请人提供）：尽管每年有近90，000名被诊断患有前列腺癌的男性最终会复发（尽管在尝试治愈性治疗后的成像研究呈阴性，但PSA升高），但对这些患者没有明确的护理标准。在这一人群中开发有效的治疗策略和挑战药物开发生态位将是重要的，因为它可以延迟转移性去势抵抗性前列腺癌（mCRPC）的发作，这是与发病率和死亡率相关的疾病阶段。该提案旨在评估治疗性癌症疫苗在这组复发性疾病患者中诱导的免疫应答，将免疫应答与临床效应（PSA动力学变化和成像转移性疾病的发展）相关联，并探索几种实验成像平台（直肠内MRI，F-18 DCFBC，Ferumoxytol增强MRI，氟化钠PET）以随访这些患者。这些扫描的结果将与常规成像研究的结果进行比较，变化将与对治疗产生免疫反应的能力相关。 患者将接受Prostvac治疗，并评估对治疗性癌症疫苗的PSA特异性免疫应答。这将通过评价T细胞对跨越PSA蛋白全长的氨基酸序列（15聚体）的反应来实现。将使用30种标志物的流式细胞术分析在外周血中评价对Prostvac的其他免疫应答，从而评价127种免疫亚群。在临床上，我们将前瞻性地确定治疗6个月后Prostvac是否会像先前试验所建议的那样减缓PSA生长动力学。此外，我们将使用实验成像平台（直肠内MRI、F-18 DCFBC、Ferumoxytol增强MRI、氟化钠PET）作为评估非转移性（通过常规骨扫描和计算机断层扫描）去势敏感性前列腺癌患者进展的方法。 如果发现治疗性癌症疫苗Prostvac可减缓前列腺癌的生长速度，则可能导致在该无症状人群中开发无毒治疗，这可能会延迟与mCRPC相关的发病率和死亡率。来自治疗患者的伴随免疫数据也可以进一步开发为生物标志物，如果它们对应于临床结果。将临床反应和常规扫描结果相关联也可能导致在其他治疗策略的开发中使用这些新的实验性成像技术

 DESCRIPTION (provided by applicant): Despite the fact that nearly 90,000 men who are diagnosed each year with prostate cancer will ultimately develop recurrence (rising PSA despite negative imaging studies after attempted curative therapy) there is no clear standard of care for these patients. Developing effective treatment strategies in this population and challenging drug development niche would be significant because it could delay the onset of metastatic castration resistant prostate cancer (mCRPC), which is the stage of disease that is associated with morbidity and mortality. This proposal is designed to evaluate the immune responses induced by a therapeutic cancer vaccine in this group of patients with recurrent disease, correlate immune responses with clinical effect (changes in PSA kinetics and development of metastatic disease on imaging) and explore several experimental imaging platforms (endorectal MRI, F-18 DCFBC, Ferumoxytol enhanced MRI, Sodium Fluoride PET) to follow these patients. The findings on these scans will be compared to the findings on conventional imaging studies and changes will be correlated with the ability to mount immune responses to treatment. Patients will be treated with Prostvac and evaluated for PSA specific immune responses to the therapeutic cancer vaccine. This will be accomplished by evaluating T-cells for response to sequences of amino acids (15-mers) that span the full length of the PSA Protein. Additional immune responses to Prostvac will be evaluated in peripheral blood using flow-cytometry analysis of 30 markers allowing for the evaluation of 127 immune subsets. Clinically, we will prospectively determine if Prostvac slows PSA growth kinetics after 6 months of treatment as has been suggested by previous trials. In addition we will use experimental imaging platforms (Endorectal MRI, F-18 DCFBC, Ferumoxytol enhanced MRI, Sodium Fluoride PET) as methods to assess progression in patients with non-metastatic (by conventional bone scan and computed tomography) castration sensitive prostate cancer. If the therapeutic cancer vaccine Prostvac is found to slow the growth rate of prostate cancer, then it could lead to the development of a non-toxic therapy in this asymptomatic population which would have the potential of delaying the morbidity and mortality associated with mCRPC. Accompanying immune data from treated patients could also be further developed as biomarkers if they correspond to clinical outcomes. Correlating clinical responses and findings on conventional scans could also lead to the use of these new experimental imaging technologies in the development of other treatment strategies