Multiepitope CD8+ T cell response to an NY-ESO-1 peptide vaccine results in imprecise tumor targeting
Multiepitope CD8+ T cell response to an NY-ESO-1 peptide vaccine results in imprecise tumor targeting
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DOI：
10.1172/jci200216428
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发表时间：
2002-12-01
影响因子：
15.9
通讯作者：
Valmori, D
中科院分区：
文献类型：
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作者：
Dutoit, V;Taub, RN;Valmori, D
癌症睾丸抗原 W-ESO-1 是癌症患者通用疫苗接种最有希望的候选抗原之一。在这里，我们分析了 CD8+ T 细胞对 NY-ESO-1 肽疫苗的反应，该疫苗由两种先前定义的肽 157-165 和 157-167 组成，与 GM-CSF 作为全身佐剂一起施用。 NY-ESO-1 肽疫苗引发了针对 157-167 区域中多个不同表位的 CD8(+) T 细胞反应，正如使用在该区域中掺入重叠 A2 结合肽的 A2/肽多聚体所揭示的那样。然而，只有一小部分诱导的CD8(+) T细胞，即那些以足够高的功能亲合力识别肽157-165的细胞，识别了NY-ESO-1(+)肿瘤细胞上自然加工的靶标。相比之下，大多数肽157-165特异性CD8(+) T细胞表现出较低的功能亲和力并且没有肿瘤反应性。此外，疫苗诱导的对157-167区域其他重叠表位具有特异性的CD8+T细胞未能显着识别表达N-Y-ESO-1的肿瘤靶标。因此，由于通过合成肽疫苗接种可以引发的 CD8(+) T 细胞库的复杂性，需要精确定义目标表位，并因此需要精确定义用作免疫原的相应肽，以确保精确的肿瘤靶向。
The cancer-testis antigen W-ESO-1 is one of the most promising candidates for generic vaccination of cancer patients. Here we analyzed the CD8+ T cell response to a NY-ESO-1 peptide vaccine composed of the two previously defined peptides 157-165 and 157-167, administered with GM-CSF as a systemic adjuvant. The NY-ESO-1 peptide vaccine elicited a CD8(+) T cell response directed against multiple distinct epitopes in the 157-167 region, as revealed by using A2/peptide multimers incorporating overlapping A2 binding peptides in this region. However, only a minor fraction of the elicited CD8(+) T cells, namely those recognizing the peptide 157-165 with sufficiently high functional avidity, recognized the naturally processed target on NY-ESO-1(+) tumor cells. In contrast, the majority of peptide 157-165-specific CD8(+) T cells exhibited lower functional avidity and no tumor reactivity. In addition, vaccine-elicited CD8(+) T cells specific for other overlapping epitopes in the 157-167 region failed to significantly recognize N-Y-ESO-1-expressing tumor targets. Thus, because of the complexity of the CD8(+) T cell repertoire that can be elicited by vaccination with synthetic peptides, a precise definition of the targeted epitope, and hence, of the corresponding peptide to be used as immunogen, is required to ensure a precise tumor targeting.