Vaccination of stage III/IV melanoma patients with long NY-ESO-1 peptide and CpG-B elicits robust CD8+ and CD4+ T-cell responses with multiple specificities including a novel DR7-restricted epitope
Vaccination of stage III/IV melanoma patients with long NY-ESO-1 peptide and CpG-B elicits robust CD8+ and CD4+ T-cell responses with multiple specificities including a novel DR7-restricted epitope
复制标题
DOI：
10.1080/2162402x.2016.1216290
复制
发表时间：
2016-01-01
期刊：
影响因子：
7.2
通讯作者：
Jandus, C.
中科院分区：
文献类型：
--
作者：
Baumgaertner, P.;Nunes, C. Costa;Jandus, C.
长的合成肽和含CpG的寡脱氧核苷酸是很有希望的癌症疫苗成分。在这项I期试验中，19名患者平均每月接种8支疫苗(范围1-12)。由合成的长NY-ESO-1(79-108)肽和CpG-B(PF-3512676)组成，在Montanide ISA-51中乳化。在18名可评估的患者中，疫苗接种诱导了抗原特异性CD8(+)和CD4(+)T细胞和抗体反应，在免疫治疗开始后早期开始，持续至少一年。无论患者的HLA如何，T细胞都能产生抗原特异性反应，分泌强烈的干扰素和肿瘤坏死因子。免疫原性最强的区域是CD8(+)T细胞的NY-ESO-1(89-102)和CD4(+)T细胞的NY-ESO-1(83-99)。我们发现了一种新的高度免疫原性的表位(HL A-DR7/NY-ESO-1(87-99))；7例HL A-DR7(+)患者产生了强烈的CD4(+)T细胞反应，用荧光多聚体直接在体外检测到。因此，人工合成的NY-ESO-1(79-108)多肽与强佐剂CpG-B联合免疫可诱导黑色素瘤患者CD8(+)和CD4(+)T细胞的整合、强健和功能性反应，支持这种免疫治疗方法的进一步发展。
Long synthetic peptides and CpG-containing oligodeoxynucleotides are promising components for cancer vaccines. In this phase I trial, 19 patients received a mean of 8 (range 1-12) monthly vaccines s.c. composed of the long synthetic NY-ESO-1(79-108) peptide and CpG-B (PF-3512676), emulsified in Montanide ISA-51. In 18/18 evaluable patients, vaccination induced antigen-specific CD8(+) and CD4(+) T-cell and antibody responses, starting early after initiation of immunotherapy and lasting at least one year. The T-cells responded antigen-specifically, with strong secretion of IFN and TNF, irrespective of patients' HLAs. The most immunogenic regions of the vaccine peptide were NY-ESO-1(89-102) for CD8(+) and NY-ESO-1(83-99) for CD4(+) T-cells. We discovered a novel and highly immunogenic epitope (HLA-DR7/NY-ESO-1(87-99)); 7/7 HLA-DR7(+) patients generated strong CD4(+) T-cell responses, as detected directly ex vivo with fluorescent multimers. Thus, vaccination with the long synthetic NY-ESO-1(79-108) peptide combined with the strong immune adjuvant CpG-B induced integrated, robust and functional CD8(+) and CD4(+) T-cell responses in melanoma patients, supporting the further development of this immunotherapeutic approach.