Phase II Clinical Trial of Multiple Peptide Vaccination for Advanced Head and Neck Cancer Patients Revealed Induction of Immune Responses and Improved OS
Phase II Clinical Trial of Multiple Peptide Vaccination for Advanced Head and Neck Cancer Patients Revealed Induction of Immune Responses and Improved OS
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DOI：
10.1158/1078-0432.ccr-14-0202
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发表时间：
2015-01-15
影响因子：
11.5
通讯作者：
Shinohara, Masanori
中科院分区：
文献类型：
--
作者：
Yoshitake, Yoshihiro;Fukuma, Daiki;Shinohara, Masanori
目的：从理想的癌症-睾丸抗原衍生的肽，包括LY 6 K、CDCA 1和IMP 3（使用全基因组cDNA微阵列分析鉴定），用于头颈部鳞状细胞癌（HNSCC）的免疫治疗。实验设计：共37例晚期HNSCC患者接受肽疫苗治疗，采用酶联免疫斑点法（ELISPOT）和五聚体法评价其OS、PFS和免疫应答。每周用IFA皮下施用肽。在晚期HNSCC.Results：我们的癌症疫苗治疗耐受性良好的基础上，对HLA-A*2402阳性[A24（+）]患者用肽疫苗治疗和阴性[A24（-）]患者不用肽疫苗治疗的差异进行了评价。A24（+）疫苗接种组（n = 37）的OS在统计学上显著长于A24（-）组（n = 18），中位生存时间（MST）分别为4.9个月和3.5个月; P < 0.05。其中一名患者表现出完全缓解。在A24（+）疫苗接种组中，ELISPOT试验分别在85.7%、64.3%和42.9%的患者中鉴定出LY 6 K-、CDCA 1-和IMP 3-特异性CTL应答。显示LY 6 K-和CDCA 1-特异性CTL应答的患者表现出比没有CTL诱导的患者更长的OS。结论：该疫苗诱导的免疫应答可能改善晚期HNSCC患者的预后。(C)2014年AACR。
Purpose: The peptides derived from ideal cancer-testis antigens, including LY6K, CDCA1, and IMP3 (identified using genome-wide cDNA microarray analyses), were used in immunotherapy for head and neck squamous cell cancer (HNSCC). In this trial, we analyzed the immune response to and safety and efficacy of vaccine therapy.Experimental Design: A total of 37 patients with advanced HNSCC were enrolled in this trial of peptide vaccine therapy, and the OS, PFS, and immunologic response were evaluated using enzyme-linked ImmunoSpot (ELISPOT) and pentamer assays. The peptides were subcutaneously administered weekly with IFA. The primary endpoints were evaluated on the basis of differences between HLA-A*2402-positive [A24(+)] patients treated with peptide vaccine therapy and -negative [A24(-)] patients treated without peptide vaccine therapy among those with advanced HNSCC.Results: Our cancer vaccine therapy was well tolerated. The OS of the A24(+) vaccinated group (n = 37) was statistically significantly longer than that of the A24(-) group (n = 18) and median survival time (MST) was 4.9 versus 3.5 months, respectively; P < 0.05. One of the patients exhibited a complete response. In the A24(+) vaccinated group, the ELISPOT assay identified LY6K-, CDCA1-, and IMP3-specific CTL responses in 85.7%, 64.3%, and 42.9% of the patients, respectively. The patients showing LY6K- and CDCA1-specific CTL responses demonstrated a longer OS than those without CTL induction. Moreover, the patients exhibiting CTL induction for multiple peptides demonstrated better clinical responses.Conclusions: The immune response induced by this vaccine may improve the prognosis of patients with advanced HNSCC. (C) 2014 AACR.