A 15-year follow-up of AJCC stage III malignant melanoma patients treated postsurgically with Newcastle disease virus (NDV) oncolysate and determination of alterations in the CD8 T cell repertoire
A 15-year follow-up of AJCC stage III malignant melanoma patients treated postsurgically with Newcastle disease virus (NDV) oncolysate and determination of alterations in the CD8 T cell repertoire
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DOI：
10.1007/bf03401771
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发表时间：
1998-12-01
影响因子：
5.7
通讯作者：
Armstrong, CA
中科院分区：
文献类型：
--
作者：
Batliwalla, FM;Bateman, BA;Armstrong, CA
背景：发展有效的辅助治疗方法治疗高危黑色素瘤患者，对于预防转移性疾病和改善患者生存至关重要。主动特异性免疫疗法已作为一种辅助治疗在许多临床试验中被测试，总体成功率有限，但偶尔有希望。新城疫病毒(NDV)溶瘤物已被用作这些患者术后治疗的辅助免疫治疗剂。1975年启动的一项第二阶段研究表明，在治疗淋巴清扫后，AJCC III期黑色素瘤患者使用由感染活新城疫病毒(NDV Oncolysate)的同种和自体人黑色素瘤细胞组成的佐剂疫苗治疗，10年内存活率为60%，没有不良反应。继续对早期结果有希望的试验进行长期分析，以及对这些患者产生的免疫学反应进行评估，可能会改善未来临床试验的治疗决策。材料和方法：在上述II期研究中，我们分析了手术后接受新城疫病毒溶瘤物治疗的患者的15年存活率。为了了解这种治疗的免疫学效果，我们还对这些患者的外周血T细胞谱系进行了全面的分析。结果：这组患者的总体15年生存率为55%。先前的研究表明，接受免疫治疗的患者预后的改善与CD8(+)CD57(+)细胞数量的增加有关。在存活的患者中，我们观察到外周血中CD8(+)T细胞群具有显著的寡克隆性，这反映了CD8(+)CD57(+)亚群的克隆性扩张。结论：新城疫瘤溶物佐剂接种与淋巴阳性恶性黑色素瘤患者的生存时间延长有关，CD8(+)T细胞可能是疗效的重要组成部分。
Background: The development of effective adjuvant therapies for the treatment of high-risk melanoma patients is critical for the prevention of metastatic disease and improvement of patient survival. Active specific immunotherapy has been tested as an adjuvant treatment in numerous clinical trials with overall limited, but occasionally promising, success rates. Newcastle disease virus (NDV) oncolysate has been utilized as an adjunctive immunotherapeutic agent in the postsurgical management of these patients. A phase II study initiated in 1975 using adjuvant vaccine therapy composed of allogeneic and autologous human melanoma cells infected with live NDV (NDV oncolysate) in patients with AJCC stage III melanoma following therapeutic lymph node dissection has shown >60% survival rate at 10 years with no adverse effects. Continued long-term analysis of trials with promising early results as well as assessment of immunologic responses generated in these patients may result in improved therapeutic decisions for clinical trials in the future.Materials and Methods: We analyzed the 15-year survival of patients treated postsurgically with NDV oncolysate in the phase II study described above. In an attempt to understand the immunological effects of this treatment, we have also carried out a comprehensive analysis of the peripheral blood T cell repertoire in these patients.Results: The overall 15-year survival of this group of patients is 55%. Previous studies have suggested that improved outcome in patients undergoing immunotherapy is correlated with increased numbers of CD8(+)CD57(+) cells. In surviving patients, we observed a striking oligoclonality in the CD8(+) T cell population in peripheral blood, which reflects clonal expansions in the CD8(+)CD57(+) subset.Conclusions: The data suggest that adjuvant vaccination with NDV oncolysates is associated with prolonged survival of patients with lymph node-positive malignant melanoma and that CD8(+) T cells may be an important component of therapeutic efficacy.