Department of Surgery, Human Immune Therapy Center, University of Virginia, Charlottesville, Virginia, USA.
Clin Cancer Res. 2013 Aug 1;19(15):4228-38. doi: 10.1158/1078-0432.CCR-13-0002. Epub 2013 May 7.
This multicenter randomized trial was designed to evaluate whether melanoma helper peptides augment cytotoxic T lymphocyte (CTL) responses to a melanoma vaccine and improve clinical outcome in patients with advanced melanoma.
One hundred seventy-five patients with measurable stage IV melanoma were enrolled into 4 treatment groups, vaccinated with 12 MHC class I-restricted melanoma peptides to stimulate CTL (12 MP, group A), plus a tetanus peptide (group B), or a mixture of 6 melanoma helper peptides (6 MHP, group C) to stimulate helper T lymphocytes (HTL), or with 6 melanoma helper peptide (6 MHP) alone (group D), in incomplete Freund's adjuvant plus granulocyte macrophage colony-stimulating factor. CTL responses were assessed using an in vitro-stimulated IFN-γ ELIspot assay, and HTL responses were assessed using a proliferation assay.
In groups A to D, respectively, CTL response rates to 12 melanoma peptides were 43%, 47%, 28%, and 5%, and HTL response rates to 6 MHP were in 3%, 0%, 40%, and 41%. Best clinical response was partial response in 7 of 148 evaluable patients (4.7%) without significant difference among study arms. Median overall survival (OS) was 11.8 months. Immune response to 6 MHP was significantly associated with both clinical response (P = 0.036) and OS (P = 0.004).
Each vaccine regimen was immunogenic, but MHPs did not augment CTL responses to 12 melanoma peptides. The association of survival and immune response to 6 MHP supports further investigation of helper peptide vaccines. For patients with advanced melanoma, multipeptide vaccines should be studied in combination with other potentially synergistic active therapies.
本多中心随机试验旨在评估黑素瘤辅助肽是否能增强细胞毒性 T 淋巴细胞（CTL）对黑素瘤疫苗的反应，并改善晚期黑素瘤患者的临床结局。
175 例可测量的 IV 期黑素瘤患者被纳入 4 个治疗组，用 12 种 MHC Ⅰ类限制性黑素瘤肽（12MP）刺激 CTL（A 组），加破伤风类毒素（B 组），或 6 种黑素瘤辅助肽（6MHP）混合物（C 组）刺激辅助性 T 淋巴细胞（HTL），或仅用 6 种黑素瘤辅助肽（6MHP）（D 组），均在不完全弗氏佐剂加粒细胞巨噬细胞集落刺激因子中接种。使用体外刺激 IFN-γ ELIspot assay 评估 CTL 反应，使用增殖assay 评估 HTL 反应。
在 A 至 D 组中，12 种黑素瘤肽的 CTL 反应率分别为 43%、47%、28%和 5%，6MHP 的 HTL 反应率分别为 3%、0%、40%和 41%。148 例可评价患者中，7 例出现部分缓解（4.7%），各研究组之间无显著差异。中位总生存期（OS）为 11.8 个月。对 6MHP 的免疫反应与临床反应（P = 0.036）和 OS（P = 0.004）均显著相关。
每种疫苗方案均具有免疫原性，但 MHPs 并未增强对 12 种黑素瘤肽的 CTL 反应。6MHP 与生存和免疫反应的相关性支持进一步研究辅助肽疫苗。对于晚期黑素瘤患者，应将多肽疫苗与其他可能具有协同作用的活性疗法联合进行研究。
