Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Int J Cancer. 2013 Apr 1;132(7):1581-91. doi: 10.1002/ijc.27819. Epub 2012 Nov 21.
We previously established safety and immunogenicity of a p53 synthetic long peptides (p53-SLP®) vaccine. In the current trial, we investigated whether combination of interferon-alpha (IFN-α) with p53-SLP® is both safe and able to improve the induced p53-specific IFN-γ response. Eleven colorectal cancer patients successfully treated for metastatic disease were enrolled in this study. Of these, nine patients completed follow-up after two injections with p53-SLP® together with IFN-α. Safety and p53-specific immune responses were determined before and after vaccination. Furthermore, cryopreserved PBMCs were compared head-to-head to cryopreserved PBMCs obtained in our previous trial with p53-SLP® only. Toxicity of p53-SLP® vaccination in combination with IFN-α was limited to Grade 1 or 2, with predominantly small ongoing swellings at the vaccination site. All patients harbored p53-specific T cells after vaccination and most patients showed p53-specific antibodies. Compared to the previous trial, addition of IFN-α significantly improved the frequency of p53-specific T cells in IFN-γ ELISPOT. Moreover, in this trial, p53-specific T cells were detectable in blood samples of all patients in a direct ex vivo multiparameter flowcytometric assay, opposed to only 2 of 10 patients vaccinated with p53-SLP® only. Finally, patients in this trial displayed a broader p53-specific immunoglobulin-G response, indicating an overall better p53-specific T-helper response. Our study shows that p53-SLP® vaccination combined with IFN-α injection is safe and capable of inducing p53-specific immunity. When compared to a similar trial with p53-SLP® vaccination alone the combination was found to induce significantly more IFN-γ producing p53-specific T cells.
我们之前已经证实了 p53 合成长肽（p53-SLP®）疫苗的安全性和免疫原性。在当前的试验中，我们研究了干扰素-α（IFN-α）与 p53-SLP®联合应用是否既安全又能增强诱导的 p53 特异性 IFN-γ 反应。11 名转移性结直肠癌患者成功接受了该治疗，其中 9 名患者在接受 p53-SLP®联合 IFN-α 两次注射后完成了随访。在接种前后，我们测定了安全性和 p53 特异性免疫反应。此外，我们对头对头比较了冷冻保存的 PBMC 与仅使用 p53-SLP®的以前试验中获得的冷冻保存的 PBMC。p53-SLP®联合 IFN-α 接种的毒性仅限于 1 级或 2 级，主要是接种部位的小持续性肿胀。所有患者在接种后均存在 p53 特异性 T 细胞，大多数患者显示出 p53 特异性抗体。与以前的试验相比，IFN-α 的加入显著提高了 IFN-γ ELISPOT 中 p53 特异性 T 细胞的频率。此外，在该试验中，与仅用 p53-SLP®接种的 10 名患者中的 2 名相比，直接在体外多参数流式细胞术检测中可以在所有患者的血液样本中检测到 p53 特异性 T 细胞。最后，该试验中的患者表现出更广泛的 p53 特异性免疫球蛋白-G 反应，表明总体上 p53 特异性 T 辅助反应更好。我们的研究表明，p53-SLP®疫苗接种联合 IFN-α 注射是安全的，能够诱导 p53 特异性免疫。与单独使用 p53-SLP®疫苗接种的类似试验相比，联合应用被发现可诱导更多的 IFN-γ 产生 p53 特异性 T 细胞。
