Uchino Yoshihiro, Muroya Daisuke, Yoshitomi Munehiro, Shichijo Shigeki, Yamada Akira, Sasada Tetsuro, Yamada Teppei, Okuda Koji, Itoh Kyogo, Yutani Shigeru
Cancer Vaccine Center, Kurume University, Kurume, Fukuoka 839-0823, Japan.
Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Mol Clin Oncol. 2021 Feb;14(2):39. doi: 10.3892/mco.2020.2201. Epub 2020 Dec 29.
The aim of the present study was to determine the factors associated with reduced clinical benefits of personalized peptide vaccination (PPV) for pancreatic cancer. Phase II PPV clinical trials comprising 309 (8 non-advanced and 301 advanced-stage) patients with pancreatic cancer were conducted. Two to four peptides were selected among a set of 31 different peptides as vaccine candidates for personalized peptide vaccination based on human leukocyte antigen types and preexisting peptide-specific IgG levels, and subcutaneously injected. The selected peptides were subcutaneously injected. Of the 309 patients, 81 failed to complete the 1st PPV cycle due to rapid disease progression, and their median overall survival [2.1 months; 95% confidence interval (CI), 1.8-2.7] was significantly shorter than that of the remaining 228 patients (8.4 months; 95% CI, 8.4-9.9; P<0.01). 'Immune boosting' was defined when IgG levels before vaccination increased more than 2-fold after vaccination. Immune boosting was observed in the majority of patients with PPV irrespective of whether or not they received concomitant chemotherapy. Additionally, patients demonstrating immune boosting exhibited longer survival rates. Although the positive-response rates and peptide-specific IgG levels in pre- and post-vaccination samples differed among the 31 peptides, patients exhibiting immune boosting in response to each of the vaccinated peptides demonstrated longer survival times. Pre-vaccination factors associated with reduced clinical benefits were high c-reactive protein (CRP) levels, high neutrophil counts, lower lymphocyte and red blood cell counts, advanced disease stage and the greater number of chemotherapy courses prior to the PPV treatment. The post-vaccination factors associated with lower clinical benefits were PPV monotherapy and lower levels of immune boosting. In conclusion, pre-vaccination inflammatory signatures, rather than pre- or post-vaccination immunological signatures, were associated with reduced clinical benefits of personalized peptide vaccination (PPV) for pancreatic cancer.
本研究的目的是确定与胰腺癌个性化肽疫苗接种（PPV）临床获益降低相关的因素。开展了包含309例（8例非晚期和301例晚期）胰腺癌患者的II期PPV临床试验。根据人类白细胞抗原类型和预先存在的肽特异性IgG水平，从31种不同的肽中选择2至4种肽作为个性化肽疫苗接种的候选疫苗，并进行皮下注射。所选肽进行皮下注射。在309例患者中，81例因疾病快速进展未能完成第1个PPV周期，其总生存期中位数为2.1个月[95%置信区间（CI），1.8 - 2.7]，显著短于其余228例患者（8.4个月；95% CI，8.4 - 9.9；P<0.01）。“免疫增强”定义为接种疫苗后IgG水平比接种前升高超过2倍。无论是否接受同步化疗，大多数接受PPV的患者都观察到了免疫增强。此外，表现出免疫增强的患者生存率更长。尽管接种前和接种后样本中的阳性反应率和肽特异性IgG水平在31种肽之间存在差异，但对每种接种肽表现出免疫增强的患者生存期更长。与临床获益降低相关的接种前因素包括高C反应蛋白（CRP）水平、高中性粒细胞计数、较低的淋巴细胞和红细胞计数、疾病晚期以及PPV治疗前更多的化疗疗程。与临床获益较低相关的接种后因素包括PPV单药治疗和较低的免疫增强水平。总之，接种前的炎症特征而非接种前或接种后的免疫特征与胰腺癌个性化肽疫苗接种（PPV）的临床获益降低相关。
