Cancer Vaccine Center, Kurume University School of Medicine, Kurume, Japan.
Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
Cancer Sci. 2018 Sep;109(9):2660-2669. doi: 10.1111/cas.13709. Epub 2018 Jul 23.
Peptide-based cancer vaccines are able to induce strong immune responses, but their clinical results are unsatisfactory. To determine clinically correlated peptides, we analyzed survival data from urological cancer patients treated by personalized peptide vaccination (PPV), in which different multiple peptides were used for individual patients based on human leukocyte antigen (HLA) type and pre-existing immunity. Survival data were obtained from a database of 265 urological cancer patients treated in 5 clinical PPV trials comprising 154 patients with castration-resistant prostate cancer (CRPC) and 111 patients with advanced urothelial cancer (UC). Expression of tumor-associated antigens (TAA) was evaluated in 10 prostate cancer tissues, 4 metastatic lymph nodes from prostate cancer, and 10 UC tissues using immunohistochemical staining. Clinical efficacy of individual peptides for overall survival was evaluated by the Cox proportional hazards regression model. All TAA coding candidate peptides used in PPV treatment were expressed in tumor cells from prostate cancer and UC samples except for p56Lck in both, and prostate-specific antigen (PSA), prostatic acid phosphatase (PAP) and prostate-specific membrane antigen (PSMA) in the UC samples. Patients with the following peptides had a significantly longer survival than patients without the peptides (hazard ratio <1.0, 95% confidence intervals <1.0 and P < .05): SART3-109, PTHrP-102, HNPRL-140, SART3-302 and Lck-90 in CRPC patients, and EGF-R-800, Lck-486, PSMA-624, CypB-129 and SART3-734 in advanced UC patients, respectively. Correlated peptides selected using both survival data and pre-existing immunity for PPV treatment may enhance the clinical benefits for urological cancer patients.
基于肽的癌症疫苗能够诱导强烈的免疫反应，但它们的临床效果并不令人满意。为了确定与临床相关的肽，我们分析了接受个体化肽疫苗接种（PPV）治疗的尿路上皮癌患者的生存数据，其中根据人类白细胞抗原（HLA）类型和预先存在的免疫，为每位患者使用不同的多种肽。生存数据来自接受 5 项临床试验中个体化肽疫苗接种治疗的 265 名尿路上皮癌患者的数据库，其中包括 154 名去势抵抗性前列腺癌（CRPC）患者和 111 名晚期膀胱癌（UC）患者。使用免疫组织化学染色评估了 10 例前列腺癌组织、4 例前列腺癌转移性淋巴结和 10 例 UC 组织中的肿瘤相关抗原（TAA）的表达。通过 Cox 比例风险回归模型评估个体肽对总生存期的临床疗效。除了两者中的 p56Lck 外，PPV 治疗中使用的所有 TAA 编码候选肽都在前列腺癌和 UC 样本的肿瘤细胞中表达，UC 样本中还包括前列腺特异性抗原（PSA）、前列腺酸性磷酸酶（PAP）和前列腺特异性膜抗原（PSMA）。与没有这些肽的患者相比，具有以下肽的患者的生存时间明显更长（风险比<1.0，95%置信区间<1.0，P<.05）：CRPC 患者中的 SART3-109、PTHrP-102、HNPRL-140、SART3-302 和 Lck-90，以及晚期 UC 患者中的 EGF-R-800、Lck-486、PSMA-624、CypB-129 和 SART3-734。用于 PPV 治疗的生存数据和预先存在的免疫选择相关肽可能会增强尿路上皮癌患者的临床获益。
