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

 描述(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(尽管在尝试治疗后影像检查为阴性，PSA仍在上升)，但对这些患者的护理没有明确的标准。在这一人群中开发有效的治疗策略并挑战药物开发利基将具有重要意义，因为它可以推迟转移性去势耐药前列腺癌(MCRPC)的发病，这是与发病率和死亡率相关的疾病阶段。本研究旨在评估治疗性肿瘤疫苗在这组复发患者中诱导的免疫反应，将免疫反应与临床疗效(PSA动力学变化和影像上转移疾病的发展)联系起来，并探索几种实验成像平台(直肠内MRI、F-18DCFBC、阿魏酸甘油酯增强MRI、氟化钠PET)来跟踪这些患者。这些扫描的结果将与传统成像研究的结果进行比较，变化将与治疗过程中安装免疫反应的能力相关。患者将接受Prostvac治疗，并对治疗性癌症疫苗进行PSA特异性免疫反应评估。这将通过评估T细胞对跨越整个PSA蛋白的氨基酸序列(15-MERS)的反应来实现。对Prostvac的额外免疫反应将在外周血液中使用30个标记的流式细胞仪分析进行评估，允许评估127个免疫亚组。临床上，我们将前瞻性地确定Prostvac是否像以前的试验所建议的那样，在治疗6个月后减缓PSA的增长动力学。此外，我们还将使用实验性成像平台(Endorecal MRI、F-18DCFBC、Ferumoxtol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)去势敏感型前列腺癌患者的进展情况的方法。如果治疗性癌症疫苗Prostvac被发现可以减缓前列腺癌的生长速度，那么它可能会导致在这一无症状人群中开发一种无毒疗法，这种疗法可能会推迟与mCRPC相关的发病率和死亡率。来自接受治疗的患者的伴随免疫数据也可以进一步发展为生物标记物，如果它们与临床结果相符的话。将临床反应和常规扫描的结果联系起来，也可能导致将这些新的实验性成像技术用于开发其他治疗策略。

 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