Development of cancer vaccines targeting the cancer/testis antigen XAGE highly-expressed in lung adenocarcinoma

分析了非小细胞肺癌（NSCLC）中针对XAGE-1b的自发免疫应答。在10%（20/200）的NSCLC患者和19%（13/69）的IIIB/IV期肺腺癌患者中观察到抗XAGE-1b抗体应答。在XAGE-1b抗体阳性患者中，88%（14/16）检测到CD 4 T细胞应答，67%（6/9）检测到CD 8 T细胞应答。这些CD 4和CD 8 T细胞对XAGE-1b的应答表明XAGE-1b抗原在NSCLC中具有强免疫原性。我们从抗体阳性患者的PBMC中建立了T细胞克隆，并确定DRB 1 *04：05限制性XAGE-1b 18-31肽作为CD 4 T细胞表位，A*02：06限制性XAGE-1b 21-29肽作为CD 8 T细胞表位。CD 4 T细胞克隆识别用合成蛋白脉冲的DC。CD 8 T细胞克隆显示出对表达XAGE-1b和适当的HLA I类等位基因的肿瘤的细胞毒性。这些发现使XAGE-1b成为肺癌疫苗的一个有希望的靶点。

The spontaneous immune responses against XAGE-1b were analyzed in non-small cell lung cancer (NSCLC). An antibody response against XAGE-1b was observed in 10% (20/200) of NSCLC patients and in 19% (13/69) of stage IIIB/IV lung adenocarcinoma. A CD4 T-cell response was detected in 88% (14/16) and a CD8 T-cell response in 67% (6/9) in the XAGE-1b antibody-positive patients. These responses of CD4 and CD8 T-cell against the XAGE-1b indicate the strong immunogenicity of the XAGE-1b antigen in NSCLC. We established T-cell clones from PBMCs of antibody-positive patients and determined the DRB1*04:05-restricted XAGE-1b 18-31 peptide as a CD4 T cell epitope and the A*02:06-restricted XAGE-1b 21-29 peptide as a CD8 T-cell epitope. The CD4 T-cell clone recognized DCs pulsed with the synthetic protein. The CD8 T-cell clone showed cytotoxicity against a tumor expressing XAGE-1b and the appropriate HLA class I allele. These findings establish XAGE-1b as a promising target for a lung cancer vaccine.