Amato Robert J, Drury Noel, Naylor Stuart, Jac Jaroslaw, Saxena Somya, Cao Amy, Hernandez-McClain Joan, Harrop Richard
Department of Genitourinary Oncology Program, The Methodist Hospital Research Institute, 6560 Fannin, Houston, TX 77047, USA.
J Immunother. 2008 Jul-Aug;31(6):577-85. doi: 10.1097/CJI.0b013e31817deafd.
The attenuated vaccinia virus, modified vaccinia Ankara, has been engineered to deliver the tumor antigen 5T4 (TroVax). TroVax has been evaluated in an open-label phase 2 trial in hormone refractory prostate cancer patients in which the vaccine was administered either alone or in combination with granulocyte macrophage-colony stimulating factor (GM-CSF). The comparative safety and immunologic and clinical efficacy of TroVax alone or in combination with GM-CSF was determined. Twenty-seven patients with metastatic hormone refractory prostate cancer were treated with TroVax alone (n=14) or TroVax+GM-CSF (n=13). 5T4-specific cellular and humoral responses were monitored throughout the study. Clinical responses were assessed by quantifying prostate-specific antigen concentrations and measuring changes in tumor burden by computer-assisted tomography scan. TroVax was well tolerated in all patients with no serious adverse events attributed to vaccination. Of 24 immunologically evaluable patients, all mounted 5T4-specific antibody responses. Periods of disease stabilization from 2 to >10 months were observed. Time to progression was significantly greater in patients who mounted 5T4-specific cellular responses compared with those who did not (5.6 vs. 2.3 mo, respectively). There were no objective clinical responses seen in this study. In this study, the combination of GM-CSF with TroVax showed similar clinical and immunologic responses to TroVax alone. The high frequency of 5T4-specific immune responses and relationship with enhanced time to progression is encouraging and warrants further investigation.
减毒痘苗病毒，即安卡拉改良痘苗病毒，已被改造用于递送肿瘤抗原5T4（TroVax）。TroVax已在一项开放标签的2期试验中对激素难治性前列腺癌患者进行了评估，该试验中疫苗单独给药或与粒细胞巨噬细胞集落刺激因子（GM-CSF）联合给药。确定了TroVax单独使用或与GM-CSF联合使用的相对安全性、免疫和临床疗效。27例转移性激素难治性前列腺癌患者接受了单独的TroVax治疗（n = 14）或TroVax + GM-CSF治疗（n = 13）。在整个研究过程中监测5T4特异性细胞和体液反应。通过定量前列腺特异性抗原浓度并通过计算机断层扫描测量肿瘤负荷的变化来评估临床反应。所有患者对TroVax耐受性良好，没有因接种疫苗导致的严重不良事件。在24例可进行免疫学评估的患者中，所有患者均产生了5T4特异性抗体反应。观察到疾病稳定期为2至10个月以上。与未产生5T4特异性细胞反应的患者相比，产生该反应的患者的疾病进展时间明显更长（分别为5.6个月和2.3个月）。本研究中未观察到客观的临床反应。在本研究中，GM-CSF与TroVax联合使用显示出与单独使用TroVax相似的临床和免疫反应。5T4特异性免疫反应的高频率以及与延长的疾病进展时间的关系令人鼓舞，值得进一步研究。
