Sato Yuji, Shomura Hiroki, Maeda Yoshiaki, Mine Takashi, Une Yoshie, Akasaka Yoshinobu, Kondo Masao, Takahashi Shusaku, Shinohara Toshiki, Katagiri Kazuko, Sato Mika, Okada Shiori, Matsui Kanae, Yamada Akira, Yamana Hideaki, Itoh Kyogo, Todo Satoru
First Department of Surgery, Hokkaido University School of Medicine, N15 W7 Sapporo, Hokkaido 060-8638, Japan.
Cancer Sci. 2003 Sep;94(9):802-8. doi: 10.1111/j.1349-7006.2003.tb01522.x.
There is no standard treatment modality for advanced gastric cancer (GC) at the present time. To develop a new treatment modality, we investigated the immunological responses of advanced GC patients (n = 13, 9 non-scirrhous and 4 scirrhous types) vaccinated with peptides to a regimen under which pre-vaccination peripheral blood mononuclear cells (PBMCs) were screened for their reactivity in vitro to each of 14 peptides on HLA-A24 or 16 peptides on -A2 allele, then only the reactive peptides (maximum: 4) were administered in vivo. This regimen was generally well tolerated, although grade I levels of fever and local skin reactions were observed in several patients. Delayed-type hypersensitivity (DTH) to the vaccinated peptides was observed in 4 patients. Increased cellular and humoral immune responses to the vaccinated peptides were observed in post-vaccination PBMCs from 4 of 8 patients and in post-vaccination sera of 8 of 10 patients tested, respectively. Prolonged survival was observed in patients showing cellular and humoral immune responses to the vaccinated peptides in the post-vaccination samples, including all 4 patients with the scirrhous type. These results encourage further development of peptide-based immunotherapy for GC patients.
目前,晚期胃癌(GC)尚无标准治疗模式。为开发一种新的治疗模式,我们研究了晚期GC患者(n = 13,9例非硬化型和4例硬化型)接种肽疫苗后的免疫反应,该方案是在接种疫苗前筛选外周血单个核细胞(PBMC),检测其体外对HLA - A24上的14种肽或 - A2等位基因上的16种肽的反应性,然后仅将反应性肽(最多4种)进行体内接种。该方案总体耐受性良好,尽管有几名患者出现了I级发热和局部皮肤反应。4名患者观察到对接种肽的迟发型超敏反应(DTH)。在分别检测的8名患者中,有4名患者接种疫苗后的PBMC以及10名患者中8名患者接种疫苗后的血清中,观察到对接种肽的细胞免疫和体液免疫反应增强。在接种疫苗后的样本中,对接种肽表现出细胞免疫和体液免疫反应的患者,包括所有4例硬化型患者,生存期延长。这些结果鼓励进一步开发针对GC患者的基于肽的免疫疗法。