医学
易普利姆玛
不利影响
内科学
肽疫苗
红斑
黑色素瘤
免疫疗法
接种疫苗
临床试验
肿瘤科
免疫系统
吲哚胺2,3-双加氧酶
免疫学
癌症
抗体
癌症研究
色氨酸
生物化学
化学
氨基酸
表位
作者
Jon Bjoern,Trine Zeeberg Iversen,Nikolaj Juul Nitschke,Mads Hald Andersen,Inge Marie Svane
出处
期刊:Cytotherapy
[Elsevier]
日期:2016-08-01
卷期号:18 (8): 1043-1055
被引量:42
标识
DOI:10.1016/j.jcyt.2016.05.010
摘要
Background aim Indoleamine 2,3-dioxygenase (IDO) is an emerging new target in cancer therapy that can be targeted with active immunotherapy (e.g. through peptide vaccination). Furthermore, IDO has been identified as a key mechanism underlying resistance to treatment with the checkpoint blocking antibody ipilimumab (ipi). Methods Ten patients with metastatic melanoma participated in a phase I first-in-human clinical study assessing safety of combining ipi with a 21-mer synthetic peptide vaccine from IDO denoted IDOlong. Secondary and tertiary end points included vaccine and clinical response. Results Treatment was generally safe and well tolerated. Vaccine related adverse reactions included grade I and II erythema, oedema and pruritus at the vaccination site, which were manageable with mild topical corticosteroids. One patient developed presumed ipi-induced colitis. It initially responded to high-dose parenteral corticosteroids but later relapsed while the patient was admitted to a local hospital, where he died after receiving suboptimal therapy. Vaccine-specific T-cell responses were detectable ex vivo in three patients. At first evaluation, five of the 10 treated patients were in stable disease, one of whom had an unconfirmed partial response. Conclusions Treatment with IDOlong synthetic peptide vaccine in combination with ipi was generally safe and without augmented toxicity. The vaccine induced readily detectable T-cell responses in a subset of patients. Treatment showed signs of clinical activity, although not exceeding efficacy of ipi alone. Results should be confirmed in a larger study.
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