Clinical Research Division of the Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
BMC Cancer. 2013 Dec 30;13:613. doi: 10.1186/1471-2407-13-613.
Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC). However, because of delayed immune responses, its clinical benefits, besides for overall survival (OS), are not well captured by the World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Several surrogate markers for evaluation of cancer vaccine, including prostate-specific antigen doubling time (PSADT), are currently sought. The purpose of this study was to assess prospectively the PSA kinetics and immune responses, as well as the efficacy, safety, and biomarkers of personalized peptide vaccination (PPV) in progressive CRPC.
One hundred patients with progressive CRPC were treated with PPV using 2-4 positive peptides from 31 candidate peptides determined by both human leukocyte antigen (HLA) class IA types and the levels of immunoglobulin G (IgG) against each peptide. The association between immune responses and PSADT as well as overall survival (OS) was studied.
PPV was safe and well tolerated in all patients with a median survival time of 18.8 months. Peptide-specific IgG and T-cell responses strongly correlated with PSADT (p < 0.0001 and p = 0.0007, respectively), which in turn showed correlation with OS (p = 0.018). Positive IgG responses and prolongation of PSADT during PPV were also significantly associated with OS (p = 0.001 and p = 0.004) by multivariate analysis.
PSADT could be an appropriate surrogate marker for evaluation of the clinical benefit of cancer vaccine. Further randomized trials are needed to confirm these results.
UMIN000001850.
癌症疫苗是治疗去势抵抗性前列腺癌（CRPC）患者的一种有吸引力的治疗方法。然而，由于免疫反应延迟，其临床益处，除了总生存期（OS）外，并没有被世界卫生组织（WHO）和实体瘤反应评价标准（RECIST）标准很好地捕捉到。目前正在寻找几种用于评估癌症疫苗的替代标志物，包括前列腺特异性抗原倍增时间（PSADT）。本研究旨在前瞻性评估个体化肽疫苗（PPV）在进展性 CRPC 中的 PSA 动力学、免疫反应以及疗效、安全性和生物标志物。
100 例进展性 CRPC 患者接受了 PPV 治疗，使用了 31 个候选肽中的 2-4 个阳性肽，这些肽是由人类白细胞抗原（HLA）IA 类和针对每个肽的 IgG 水平共同确定的。研究了免疫反应与 PSADT 以及总生存期（OS）之间的关系。
所有患者均能耐受 PPV，中位生存时间为 18.8 个月。肽特异性 IgG 和 T 细胞反应与 PSADT 呈强相关性（p<0.0001 和 p=0.0007），而 PSADT 又与 OS 相关（p=0.018）。在多变量分析中，PPV 期间 IgG 阳性反应和 PSADT 延长也与 OS 显著相关（p=0.001 和 p=0.004）。
PSADT 可能是评估癌症疫苗临床获益的合适替代标志物。需要进一步的随机试验来证实这些结果。
UMIN000001850。
