Karanikas Vaios, Lurquin Christophe, Colau Didier, van Baren Nicolas, De Smet Charles, Lethé Bernard, Connerotte Thierry, Corbière Véronique, Demoitié Marie-Ange, Liénard Danielle, Dréno Brigitte, Velu Thierry, Boon Thierry, Coulie Pierre G
Cellular Genetics Unit, Institute of Cellular Pathology, Université de Louvain, Brussels, Belgium.
J Immunol. 2003 Nov 1;171(9):4898-904. doi: 10.4049/jimmunol.171.9.4898.
We have analyzed the T cell responses of HLA-A1 metastatic melanoma patients with detectable disease, following vaccination with a recombinant ALVAC virus, which bears short MAGE-1 and MAGE-3 sequences coding for antigenic peptides presented by HLA-A1. To evaluate the anti-MAGE CTL responses, we resorted to antigenic stimulation of blood lymphocytes under limiting dilution conditions, followed by tetramer analysis and cloning of the tetramer-positive cells. The clones were tested for their specific lytic ability and their TCR sequences were obtained. Four patients who showed tumor regression were analyzed, and an anti-MAGE-3.A1 CTL response was observed in three of these patients. Postvaccination frequencies of anti-MAGE-3.A1 CTL were 3 x 10(-6), 3 x 10(-3), and 3 x 10(-7) of the blood CD8 T cells, respectively. These three responses were monoclonal. No anti-MAGE-1.A1 CTL response was observed. These results indicate that, like peptide immunization, ALVAC immunization produces monoclonal responses. They also suggest that low-level antivaccine CTL responses can initiate a tumor regression process. Taken together, our analysis of anti-MAGE-3.A1 T cell responses following peptide or ALVAC vaccination shows a degree of correlation between CTL response and tumor regression, but firm conclusions will require larger numbers.
我们分析了疾病可检测的HLA - A1转移性黑色素瘤患者在接种携带短MAGE - 1和MAGE - 3序列（编码由HLA - A1呈递的抗原肽）的重组ALVAC病毒后的T细胞反应。为了评估抗MAGE细胞毒性T淋巴细胞（CTL）反应，我们在有限稀释条件下对血液淋巴细胞进行抗原刺激，随后进行四聚体分析并克隆四聚体阳性细胞。检测这些克隆的特异性裂解能力并获取其T细胞受体（TCR）序列。分析了四名出现肿瘤消退的患者，其中三名患者观察到了抗MAGE - 3.A1 CTL反应。接种疫苗后抗MAGE - 3.A1 CTL在血液CD8 T细胞中的频率分别为3×10⁻⁶、3×10⁻³和3×10⁻⁷。这三种反应都是单克隆的。未观察到抗MAGE - 1.A1 CTL反应。这些结果表明，与肽免疫一样，ALVAC免疫产生单克隆反应。它们还表明低水平的抗疫苗CTL反应可以启动肿瘤消退过程。综上所述，我们对肽或ALVAC疫苗接种后抗MAGE - 3.A1 T细胞反应的分析显示CTL反应与肿瘤消退之间存在一定程度的相关性，但得出确凿结论还需要更多的数据。
