Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival
Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival
复制标题
DOI：
10.1038/nm.2883
复制
发表时间：
2012-08-01
期刊：
影响因子：
82.9
通讯作者：
Singh-Jasuja, Harpreet
中科院分区：
文献类型：
--
作者：
Walter, Steffen;Weinschenk, Toni;Singh-Jasuja, Harpreet
IMA 901是第一种用于肾细胞癌（RCC）的治疗性疫苗，由多种肿瘤相关肽（TUMAP）组成，证实在人类癌症组织中天然存在。我们在两个连续的研究中用IMA 901治疗了总共96名患有晚期RCC的人类白细胞抗原A（HLA-A）*02（+）受试者。在1期研究中，患者对多种TUMAP的T细胞应答与更好的疾病控制和更低的疫苗前叉头盒P3（FOXP 3）（+）调节性T（T-reg）细胞数量相关。随机2期试验表明，单剂量环磷酰胺减少了T-reg细胞的数量，并证实了对多种TUMAP的免疫应答与更长的总生存期相关。此外，在6个预定义的骨髓源性抑制细胞群体中，2个是总生存期的预后，在300多个血清生物标志物中，我们鉴定了载脂蛋白A-I（APOA 1）和趋化因子（C-C基序）配体17（CCL 17）作为对IMA 901的免疫应答和总生存期的预测。一项旨在确定IMA 901治疗临床获益的随机III期研究正在进行中。
IMA901 is the first therapeutic vaccine for renal cell cancer (RCC) consisting of multiple tumor-associated peptides (TUMAPs) confirmed to be naturally presented in human cancer tissue. We treated a total of 96 human leukocyte antigen A (HLA-A)*02(+) subjects with advanced RCC with IMA901 in two consecutive studies. In the phase 1 study, the T cell responses of the patients to multiple TUMAPs were associated with better disease control and lower numbers of prevaccine forkhead box P3 (FOXP3)(+) regulatory T (T-reg) cells. The randomized phase 2 trial showed that a single dose of cyclophosphamide reduced the number of T-reg cells and confirmed that immune responses to multiple TUMAPs were associated with longer overall survival. Furthermore, among six predefined populations of myeloid-derived suppressor cells, two were prognostic for overall survival, and among over 300 serum biomarkers, we identified apolipoprotein A-I (APOA1) and chemokine (C-C motif) ligand 17 (CCL17) as being predictive for both immune response to IMA901 and overall survival. A randomized phase 3 study to determine the clinical benefit of treatment with IMA901 is ongoing.