Multiple antigen-engineered DC vaccines with or without IFNα to promote antitumor immunity in melanoma
Multiple antigen-engineered DC vaccines with or without IFNα to promote antitumor immunity in melanoma
复制标题
DOI：
10.1186/s40425-019-0552-x
复制
发表时间：
2019-04-24
影响因子：
10.9
通讯作者：
Kirkwood, John M.
中科院分区：
文献类型：
--
作者：
Butterfield, Lisa H.;Vujanovic, Lazar;Kirkwood, John M.
背景：肿瘤疫苗旨在促进全身抗肿瘤免疫和肿瘤根除。肿瘤疫苗接种结合其他干预措施可能更有效。方法：基于我们之前的临床和体外研究，我们设计了一项抗原工程DC疫苗试验，以促进针对三种共同黑色素瘤抗原的多克隆CD8(+)和CD4(+)T细胞应答。结果：根据RECIST 1.1，在可测量疾病的患者中，最终的临床结果为2例部分缓解，8例稳定，14例进展。在11例手术治疗的无疾病证据(NED)的患者中，4例在中位数3年的随访中仍保持NED。大多数接种疫苗的患者表现出疫苗抗原特异性CD8(+)和CD4(+)T细胞反应增加。在这项试验中，添加干扰素α似乎没有改善免疫或临床反应。DC疫苗的检测表明，IL-12p70的分泌与免疫或临床反应无关。深入的免疫生物标志物研究支持循环Treg和MDSC在抗原特异性T细胞应答中的重要性，以及循环CD8(+)和CD4(+)T细胞亚群在临床应答中的重要性。结论：DC疫苗是促进抗肿瘤免疫的安全可靠的平台。这种联合服用一个月的大剂量干扰素并没有改善结果。血液中的免疫生物标记物分析确定了几个预测和预后生物标记物，用于进一步分析，包括MDSC。
Background: Cancer vaccines are designed to promote systemic antitumor immunity and tumor eradication. Cancer vaccination may be more efficacious in combination with additional interventions that may build on or amplify their effects.Methods: Based on our previous clinical and in vitro studies, we designed an antigen-engineered DC vaccine trial to promote a polyclonal CD8(+) and CD4(+) T cell response against three shared melanoma antigens. The 35 vaccine recipients were then randomized to receive one month of high-dose IFN alpha or observation.Results: The resulting clinical outcomes were 2 partial responses, 8 stable disease and 14 progressive disease among patients with measurable disease using RECIST 1.1, and, of 11 surgically treated patients with no evidence of disease (NED), 4 remain NED at a median follow-up of 3 years. The majority of vaccinated patients showed an increase in vaccine antigen-specific CD8(+) and CD4(+) T cell responses. The addition of IFN alpha did not appear to improve immune or clinical responses in this trial. Examination of the DC vaccine profiles showed that IL-12p70 secretion did not correlate with immune or clinical responses. In depth immune biomarker studies support the importance of circulating Treg and MDSC for development of antigen-specific T cell responses, and of circulating CD8(+) and CD4(+) T cell subsets in clinical responses.Conclusions: DC vaccines are a safe and reliable platform for promoting antitumor immunity. This combination with one month of high dose IFN alpha did not improve outcomes. Immune biomarker analysis in the blood identified several predictive and prognostic biomarkers for further analysis, including MDSC.