Vaccination with predesignated or evidence-based peptides for patients with recurrent gynecologic cancers
Vaccination with predesignated or evidence-based peptides for patients with recurrent gynecologic cancers
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DOI：
10.1097/00002371-200401000-00006
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发表时间：
2004-01-01
影响因子：
3.9
通讯作者：
Kamura, T
中科院分区：
文献类型：
--
作者：
Tsuda, N;Mochizuki, K;Kamura, T
对复发性妇科癌症患者进行了两项不同的肽疫苗接种试验。在第一个方案中，四名HLA-A24（+）患者（两名宫颈癌患者和两名卵巢癌患者）接种了疫苗前预先指定的肽。3例患者出现I级不良反应，所有患者均未观察到临床反应。在第二种方案中，6名HLA-A24（+）和4名HLA-A2（+）患者（5名患有宫颈癌，1名患有子宫内膜癌，1名患有子宫肉瘤，3名患有卵巢癌）用肽（最多4名）接种疫苗，在接种疫苗之前确认外周中预先存在细胞毒性T淋巴细胞前体。使用该方案，在8名患者中观察到I级不良反应，在1名患者中观察到2级不良反应，在1名患者中观察到3级不良反应（即直肠出血）。然而，该方案能够增强10例患者中7例的肽特异性细胞毒性T淋巴细胞，5例宫颈癌患者中3例显示客观肿瘤消退。免疫球蛋白G-反应的肽管理的分析表明，肽特异性免疫球蛋白G的诱导与临床反应。总体而言，这些结果表明，肽疫苗接种的患者显示预先存在的肽特异性细胞毒性T淋巴细胞前体的证据可能上级与预先指定的肽疫苗接种，并以证据为基础的方案是适用于临床试验中的复发性妇科癌症患者的治疗。
Two different trials of peptide vaccination were conducted for patients with recurrent gynecologic cancers. In the first regimen, four HLA-A24(+) patients (two with cervical cancer and two with ovarian cancer) were vaccinated with peptides that were predesignated before vaccination. Three patients exhibited with a grade I adverse effect, and no clinical response was observed in any patients. In the second regimen, six HLA-A24(+) and four HLA-A2(+) patients (five with cervical cancer, one with endometrial cancer, one with uterine sarcoma, and three with ovarian cancer) were vaccinated with peptides (maximum four) to which preexisting cytotoxic T lymphocyte precursors in the periphery were confirmed before vaccination. With this regimen, grade I adverse effects were observed in eight patients, a grade 2 adverse effect in one patient, and a grade 3 adverse effect (ie, rectal bleeding) in one patient. However, this regimen was able to enhance peptide-specific cytotoxic T lymphocytes in seven of ten patients, and three of five cervical cancer patients showed objective tumor regression. Analysis of immunoglobulin G-reactive to administered peptides suggested that the induction of peptide-specific immunoglobulin G was correlated with clinical responses. Overall, these results suggest that peptide vaccination of patients showing evidence of preexisting peptide-specific cytotoxic T lymphocyte precursors could be superior to vaccination with predesignated peptides, and that the evidence-based regimen is applicable for clinical trials in treatment of patients with recurrent gynecologic cancers.