A phase I study of personalized peptide vaccination for advanced urothelial carcinoma patients who failed treatment with methotrexate, vinblastine, adriamycin and cisplatin
A phase I study of personalized peptide vaccination for advanced urothelial carcinoma patients who failed treatment with methotrexate, vinblastine, adriamycin and cisplatin
复制标题
DOI：
10.1111/j.1464-410x.2010.09933.x
复制
发表时间：
2011-09-01
影响因子：
4.5
通讯作者：
Itoh, Kyogo
中科院分区：
文献类型：
--
作者：
Matsumoto, Kazumasa;Noguchi, Masanori;Itoh, Kyogo
目的探讨甲氨蝶呤、长春碱、阿霉素和顺铂（MVAC）治疗失败的晚期尿路上皮癌（UC）患者每周一次给予个性化肽疫苗（PPV）连续12周的安全性和免疫应答。10名患有MVAC难治性晚期或转移性UC的患者用每周一次的个性化肽疫苗治疗12次，使用选自具有人白细胞抗原A24和A2的患者中的14和16种肽的阳性肽，通过干扰素-γ产生和肽反应性免疫球蛋白G（IgG），使用酶-在治疗过程中监测连接的免疫吸附测定。肽疫苗接种是安全的，耐受性良好，没有主要的副作用。8例患者免疫后血清细胞毒性T淋巴细胞反应增强，抗肽IgG滴度升高，临床应答1例完全应答，1例部分应答，2例病情稳定，6例病情进展，中位无进展生存期和总生存期分别为3.0和8.9个月。在四个应答者，中位无进展生存期和总生存期分别为21和24 months，respectively. CONCLUSIONSSThis I期研究显示的安全性和增强免疫反应，在响应PPV晚期UC。潜在的疗效连续12周接种PPV在晚期UC患者值得进一步调查基于这些发现。
OBJECTIVETo investigate the safety and immune responses of 12 consecutive weeks of once-weekly personalized peptide vaccine (PPV) administration in patients with advanced urothelial carcinoma (UC) for whom therapy with methotrexate, vinblastine, adriamycin and cisplatin (MVAC) has failed.PATIENTS AND METHODSA phase I trial was designed. Ten patients with MVAC-refractory advanced or metastatic UC were treated with weekly personalized peptide vaccine 12 times using positive peptides chosen from 14 and 16 peptides in patients with human leucocyte antigens A24 and A2, respectively.Peptide-specific cytotoxic T lymphocyte precursor analysis by interferon-gamma production and peptide-reactive immunoglobulin G (IgG) using an enzyme-linked immunosorbent assay was monitored during the treatment.RESULTSThe peptide vaccination was safe and well tolerated with no major adverse effects. Increased cytotoxic T lymphocyte response and the anti-peptide IgG titre were revealed by the post-vaccination sera in eight patients.Clinical responses were as follows: one complete response, one partial response, two stable disease and six progressive disease.Median progression-free survival and overall survival were 3.0 and 8.9 months, respectively. In the four responders, median progression-free survival and overall survival were 21 and 24 months, respectively.CONCLUSIONSThis phase I study showed the safety of and boosted immune responses in response to PPV for advanced UC.The potential efficacy of 12 consecutive weekly vaccinations with PPV in patients with advanced UC merits further investigation based on these findings.