Monoclonal anti-MAGE-3 CTL responses in melanoma patients displaying tumor regression after vaccination with a recombinant canarypox virus
Monoclonal anti-MAGE-3 CTL responses in melanoma patients displaying tumor regression after vaccination with a recombinant canarypox virus
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DOI：
10.4049/jimmunol.171.9.4898
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发表时间：
2003-11-01
影响因子：
4.4
通讯作者：
Coulie, PG
中科院分区：
文献类型：
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作者：
Karanikas, V;Lurquin, C;Coulie, PG
我们分析了患有可检测疾病的 HLA-A1 转移性黑色素瘤患者在接种重组 ALVAC 病毒后的 T 细胞反应，该病毒具有编码 HLA-A1 呈递的抗原肽的短 MAGE-1 和 MAGE-3 序列。为了评估抗 MAGE 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，然后进行四聚体分析和四聚体阳性细胞的克隆。测试克隆的特异性裂解能力并获得它们的TCR序列。对四名显示肿瘤消退的患者进行了分析，并在其中三名患者中观察到抗 MAGE-3.A1 CTL 反应。免疫后血液CD8 T细胞抗MAGE-3.A1 CTL的频率分别为3 x 10(-6)、3 x 10(-3)和3 x 10(-7)。这三种反应是单克隆的。没有观察到抗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。他们还表明，低水平的抗疫苗 CTL 反应可以启动肿瘤消退过程。总而言之，我们对肽或 ALVAC 疫苗接种后的抗 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，但确切的结论需要更大的数字。
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.