Department of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Fukuoka, Japan.
Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Clin Immunol. 2016 May;166-167:48-58. doi: 10.1016/j.clim.2016.03.015. Epub 2016 Apr 9.
We designed a phase I trial to investigate the safety, immune responses and clinical benefits of a five-peptide cancer vaccine in combination with chemotherapy. Study subjects were patients positive for HLA-A2402 with locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer. Eighteen patients including nine cases of colorectal cancer were treated with escalating doses of cyclophosphamide 4days before vaccination. Five HLA-A2402-restricted, tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1 and MPHOSPH1 were injected weekly for 4weeks. Treatment was well tolerated without any adverse events above grade 3. Analysis of peripheral blood lymphocytes showed that the number of regulatory T cells dropped from baseline after administration of cyclophosphamide and confirmed that TAA-specific T cell responses were associated significantly with longer overall survival. This phase I clinical trial demonstrated safety and promising immune responses that correlated with vaccine-induced T-cell responses. Therefore, this approach warrants further clinical studies.
我们设计了一项 I 期临床试验，以研究一种由五个肽组成的癌症疫苗与化疗联合使用的安全性、免疫反应和临床获益。研究对象为 HLA-A2402 阳性、局部晚期、转移性和/或复发性胃肠道、肺或宫颈癌患者。18 名患者（包括 9 例结直肠癌患者）在接种疫苗前 4 天接受环磷酰胺递增剂量治疗。每周注射 5 种 HLA-A2402 限制性、肿瘤相关抗原（TAA）表位肽，来自 KOC1、TTK、URLC10、DEPDC1 和 MPHOSPH1，共 4 周。治疗耐受性良好，无任何 3 级以上不良事件。外周血淋巴细胞分析显示，环磷酰胺给药后调节性 T 细胞数量从基线下降，并证实 TAA 特异性 T 细胞反应与更长的总生存期显著相关。这项 I 期临床试验显示了安全性和有希望的免疫反应，与疫苗诱导的 T 细胞反应相关。因此，这种方法值得进一步的临床研究。
