Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine
Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine
复制标题
DOI：
10.1038/sj.cgt.7700937
复制
发表时间：
2006-06-01
影响因子：
6.4
通讯作者：
Rosales, R.
中科院分区：
文献类型：
--
作者：
Garcia-Hernandez, E.;Gonzalez-Sanchez, J. L.;Rosales, R.
人乳头瘤病毒（HPV）是宫颈癌的病原体。在墨西哥，每2小时就有一名妇女死亡，并且自1990年以来的统计数据显示，死亡人数不断增加。我们进行了一项 II 期临床试验，以评估 MVA E2 重组痘苗病毒在治疗与致癌乳头瘤病毒相关的高级病变（CIN 2 和 CIN 3）方面的潜在用途。 54 名具有高度病变的女性患者接受了 MVA E2 治疗性疫苗或锥切术的治疗。 34 名女性接受了治疗性疫苗，每剂总共 10(7) 个病毒颗粒，每周一次直接注射到子宫中，持续 6 周。二十名对照患者接受锥切术治疗。通过阴道镜检查，34 名患者中有 19 名没有发现病变，其中 3 名患者的病变缩小了 85-90%，另外 8 名患者的病变缩小了 60%，另外 4 名患者的病变缩小了 25%。组织学分析显示，在接受 MVA E2 治疗后，34 名患者中有 20 名高度病变完全消除。 11 名患者的病灶大小减少了 50%。在另外两名患者中，病变降至 CIN 2，而在另一名患者中，病变降至低级别（CIN 1）。所有患者都产生了针对 MVA E2 疫苗的抗体，并对乳头状瘤转化细胞产生了特异性细胞毒性反应。 MVA E2 治疗患者的 DNA 病毒载量显着降低。锥切术消除了 80% 患者的病灶，但患者没有产生针对癌细胞的特异性细胞毒活性，也没有消除乳头瘤病毒。此外，3名接受锥切术治疗的患者1年后病灶复发。这些结果表明，MVA E2 治疗性疫苗接种在刺激针对乳头瘤病毒的免疫系统以及使高度病变消退方面非常有效。
Human papillomavirus (HPV) is the etiologic agent for cervical cancer. In Mexico, a women dies every 2 h, and since 1990 the statistics have shown that the numbers of deaths are increasing. We conducted a phase II clinical trial to evaluate the potential use of the MVA E2 recombinant vaccinia virus in treating high-grade lesions (CIN 2 and CIN 3) associated with oncogenic papillomavirus. Fifty-four female patients with high degree lesions were treated either with an MVA E2 therapeutic vaccine or with conization. Thirty-four women received the therapeutic vaccine, at a total of 10(7) virus particles per dose injected directly into the uterus once every week over a 6-week period. Twenty control patients were treated with conization. By colposcopy, 19 patients out of 34 showed no lesion, in three patients the lesions were reduced by 85-90%, in eight other lesions had reduced by 60%, and in four more patients, they were reduced by 25%. Histological analysis showed total elimination of high-grade lesions in 20 out of 34 patients after treatment with MVA E2. Eleven patients had a 50% reduction in lesion size. In two other patients, the lesion was reduced to CIN 2 and in one more patient the lesion was reduced to low grade ( CIN 1). All patients developed antibodies against the MVA E2 vaccine, and generated a specific cytotoxic response against papilloma-transformed cells. DNA viral load was significantly reduced in MVA E2-treated patients. Conization eliminated the lesions in 80% of the patients, but patients did not develop cytotoxic activity specific against cancer cells and did not eliminate the papillomavirus. In addition, three patients treated with conization had recurrence of lesions 1 year later. These results show that therapeutic vaccination with MVA E2 proved to be very effective in stimulating the immune system against papillomavirus, and in generating regression of high-grade lesion.