Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+T cell response in patients with metastatic esophageal squamous cell carcinoma
Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+T cell response in patients with metastatic esophageal squamous cell carcinoma
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DOI：
10.1111/j.1349-7006.2010.01732.x
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发表时间：
2010-12-01
期刊：
影响因子：
5.7
通讯作者：
Yamaue, Hiroki
中科院分区：
文献类型：
--
作者：
Iwahashi, Makoto;Katsuda, Masahiro;Yamaue, Hiroki
有效的辅助作用是基于多肽的疫苗有效诱导抗肿瘤免疫反应对抗晚期癌症所必需的。用新的肿瘤-睾丸抗原LY6K和TTK表位多肽与CpG-7909(NCT00669292)联合应用于人类白细胞抗原A*2402携带者进行了晚期食管鳞癌的I期试验。本研究探讨了诱导肿瘤抗原特异性免疫反应的可行性和毒性。9例患者在每个28天治疗周期的第1、8、15、22天分别接种LY6K-177、TTK-567和CpG-7909多肽(1级、0级、2级、0.02级、3级；0.1 mg/kg)，均可耐受。在每种水平的三名患者中，有两名患者的PBMC中检测到了LY6K特异性T细胞反应。特别是，2/3级的两名患者表现出强烈的LY6K特异性T细胞反应。相比之下，只有两名2/3级的患者表现出TTK-567特异性T细胞反应。LY6K-177或TTK-567特异性CD8+T细胞频率在2/3级(CpG)患者中升高。多肽和CpG-7909联合免疫可增加和激活树突状细胞和自然杀伤细胞，并提高血清中α-干扰素水平。无完全缓解(CR)和部分缓解(PR)，1级1例，2/3级4例，病情稳定(SD)。综上所述，LY6K-177和TTK-567联合CpG-7909免疫成功地诱导了抗原特异性CD8+T细胞应答，增强了晚期食管鳞癌患者的天然免疫功能。因此，建议对该疫苗方案进行进一步的第二阶段试验。(《癌症科学》2010；101：2510-2517)。
Potent helper action is necessary for peptide-based vaccines to efficiently induce antitumor immune responses against advanced cancer. A phase I trial for advanced esophageal squamous cell carcinoma was carried out for patients with HLA-A*2402 using epitope peptides derived from novel cancer-testis antigens, LY6K and TTK, in combination with CpG-7909 (NCT00669292). This study investigated the feasibility and the toxicity as well as induction of tumor antigen-specific immune responses. Nine patients were vaccinated on days 1, 8, 15, and 22 of each 28-day treatment cycle with peptide LY6K-177, peptide TTK-567, and CpG-7909 (level-1; 0, level-2; 0.02, level-3; 0.1 mg/kg) and all were tolerated by this treatment. LY6K-specific T cell responses in PBMCs were detected in two of the three patients in each level. In particular, two patients in level-2/3 showed potent LY6K-specific T cell responses. In contrast, only two patients in level-2/3 showed TTK-567-specific T cell responses. The frequency of LY6K-177 or TTK-567-specific CD8+ T cells increased in patients in level-2/3 (with CpG). The vaccination with peptides and CpG-7909 increased and activated both plasmacytoid dentritic cells and natural killer cells, and increased the serum level of alpha-interferon. There were no complete response (CR) and partial response (PR), however, one of three patients in level-1, and four of six patients in level-2/3 showed stable disease (SD). In conclusion, vaccination with LY6K-177 and TTK-567 in combination with CpG-7909 successfully elicited antigen-specific CD8+ T cell responses and enhanced the innate immunity of patients with advanced esophageal squamous cell carcinoma. This vaccine protocol is therefore recommended to undergo further phase II trials. (Cancer Sci 2010; 101: 2510-2517).