Fujiwara Yoshiyuki, Okada Kaoru, Omori Takeshi, Sugimura Keijiro, Miyata Hiroshi, Ohue Masayuki, Kobayashi Shogo, Takahashi Hidenori, Nakano Hiroyuki, Mochizuki Chie, Shimizu Katsuji, Yano Masahiko, Nakamura Yusuke, Mori Masaki, Doki Yuichiro
Department of Surgery, Division of Surgical Oncology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan.
Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
Int J Oncol. 2017 May;50(5):1655-1662. doi: 10.3892/ijo.2017.3955. Epub 2017 Apr 6.
We performed a clinical trial using HLA-A24-binding peptide vaccines containing a combination of novel cancer-testis antigens and anti-angiogenic peptides for advanced gastric cancer (GC). Thirty-five GC patients who had shown resistance to the standard therapy were enrolled in this clinical trial using vaccinations with a mixture of multiple peptides derived from DEPDC1, URLC10, FoxM1, Kif20A and VEGFR1. The safety, the overall survival (OS), and the immunological responses based on an ELISPOT assay were determined to assess differences in patients who were HLA-A24-positive [24(+)] and HLA-A24-negative [24(-)]. No severe adverse effects were observed except for severe skin reactions in 4 patients. The differences in OS were not significant between patients who were 24(+) and 24(-). In the 24(+) group, patients who showed T cell responses specific to antigen peptides had a tendency towards better survival than those who showed no response, especially to the DEPDC1 peptide. The patients with local skin reactions had significantly better OS than the others. Peptide vaccine therapy was found to be safe and is expected to induce specific T cell responses in patients with advanced GC. The survival benefit of peptide vaccine monotherapy may not have been shown and further trials are needed to confirm these results.
我们开展了一项临床试验，使用包含新型癌胚抗原和抗血管生成肽组合的HLA - A24结合肽疫苗治疗晚期胃癌（GC）。35例对标准疗法耐药的GC患者参与了该临床试验，使用源自DEPDC1、URLC10、FoxM1、Kif20A和VEGFR1的多种肽混合物进行疫苗接种。基于ELISPOT试验确定安全性、总生存期（OS）和免疫反应，以评估HLA - A24阳性[24(+)]和HLA - A24阴性[24(-)]患者之间的差异。除4例患者出现严重皮肤反应外，未观察到严重不良反应。24(+)和24(-)患者的OS差异不显著。在24(+)组中，对抗原肽表现出T细胞反应的患者比无反应的患者有更好的生存趋势，尤其是对DEPDC1肽。出现局部皮肤反应的患者OS明显优于其他患者。发现肽疫苗疗法是安全的，有望在晚期GC患者中诱导特异性T细胞反应。肽疫苗单药治疗的生存获益可能尚未显现，需要进一步试验来证实这些结果。
