背景:IMA901是第一个治疗肾细胞癌(RCC)的疫苗。它含有多种天然存在于人类癌症中的肿瘤相关肽(TUMAP)。
方法:在I/II期研究中,我们共治疗了10例日本晚期RCC患者,这些患者为人类白细胞抗原A(HLA-A)*02+.疫苗接种涉及注射GM-CSF(75μg),随后在15-30分钟内i.d.注射IMA901(含有413μg每种肽)。在进入试验前4周内不允许用抗癌剂或免疫抑制剂治疗。患者计划在治疗的前5周内(诱导期)接受7次疫苗接种,然后以3周的间隔再接种10次,为期30周(维持期)。主要终点是安全性和耐受性,而次要终点是PFS,操作系统,和免疫原性。
结果:在研究期间没有治疗相关的严重不良事件或死亡。当4个月后评估反应时,10%的患者表现出部分反应,80%的人病情稳定,10%患有进行性疾病。在分析T细胞反应的患者中,5例患者对至少一种I类HLA限制性TUMAP表现出疫苗诱导的T细胞应答,2例患者对多种TUMAP表现出T细胞应答.PFS为5.5个月,OS为18个月。
结论:这项研究证明了IMA901疫苗在日本RCC患者中的安全性和耐受性,还表明疫苗接种引发了免疫反应。
IMA901 is the first therapeutic vaccine for renal cell cancer (RCC). It contains multiple tumor-associated peptides (TUMAPs) that are naturally present in human cancers.
In a phase I/II study, we treated a total of 10 Japanese patients with advanced RCC who were human leukocyte antigen A (HLA-A)*02 +. Vaccination involved i.d. injection of GM-CSF (75 μg), followed within 15-30 min by i.d. injection of
IMA901 (containing 413 μg of each peptide). No treatment with either anticancer agents or immunosuppressants was allowed within 4 weeks before entering the trial. Patients were scheduled to receive 7 vaccinations during the first 5 weeks of treatment (induction period), followed by 10 further vaccinations at 3-week intervals for up to 30 weeks (maintenance period). The primary endpoints were safety and tolerability, while the secondary endpoints were PFS, OS, and immunogenicity.
There were no treatment-related serious adverse events or deaths during the study period. When the response was assessed after 4 months, 10% of patients showed a partial response, 80% had stable disease, and 10% had progressive disease. Among patients in whom the T-cell response was analyzed, five patients showed a vaccine-induced T-cell response against at least one HLA class I-restricted TUMAP and two patients had T-cell responses to multiple TUMAPs. PFS was 5.5 months and OS was 18 months.
This study demonstrated the safety and tolerability of
IMA901 vaccine in Japanese RCC patients, and also showed that vaccination elicited an immune response.