SAGE1: a Potential Target Antigen for Lung Cancer T-Cell Immunotherapy

A fundamental understanding of cancer-specific antigens is crucial for successful T-cell immunotherapy. Sarcoma antigen 1 (SAGE1) is a cancer/testis antigen that has not yet been verified for T-cell immunotherapy applications. Here, we examined SAGE1 RNA expression and carried out IHC analyses, revealing that SAGE1 is expressed in 50% of non-small cell lung-cancer samples (n = 40). To verify the immunogenicity of SAGE1, we discovered a novel HLA-A*24:02 (HLA-A24)-restricted SAGE1 epitope (SAGE1597-606, VFSTAPPAFI) using mass spectrometry and identified SAGE1597-606-specific T-cell clones and T-cell receptors (TCR) from peripheral bloods of HLA-A24+ donors. The highest affinity TCR VF3 (KD = 4.3 μM) demonstrated the highest antitumor potency. Moreover, VF3-transduced T cells mediated the efficient killing of HLA-A24+/SAGE1+ tumor cells in vitro and effectively inhibited the growth of lung cancer xenografts in mice. Together, our data suggest that SAGE1 could be a target for T-cell immunotherapies against lung cancer, while its specific TCRs could be candidates for developing reagents to treat SAGE1+ tumors.
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Yajing Zhang #, Xiaohong Yu #, Qiuping Liu, Haiping Gong, An-An Chen, Hongjun Zheng, Shi Zhong, Yi Li

  • Mol Cancer Ther
  • 37.3
  • 2021 Nov;20(11):2302-2313.
  • Human
  • Elispot
  • 呼吸系统
  • 呼吸系统
  • T细胞
  • 肺癌
  • IFN-γ

相关货号

LXEHS01-1

Abstract

A fundamental understanding of cancer-specific antigens is crucial for successful T-cell immunotherapy. Sarcoma antigen 1 (SAGE1) is a cancer/testis antigen that has not yet been verified for T-cell immunotherapy applications. Here, we examined SAGE1 RNA expression and carried out IHC analyses, revealing that SAGE1 is expressed in 50% of non-small cell lung-cancer samples (n = 40). To verify the immunogenicity of SAGE1, we discovered a novel HLA-A*24:02 (HLA-A24)-restricted SAGE1 epitope (SAGE1597-606, VFSTAPPAFI) using mass spectrometry and identified SAGE1597-606-specific T-cell clones and T-cell receptors (TCR) from peripheral bloods of HLA-A24+ donors. The highest affinity TCR VF3 (KD = 4.3 μM) demonstrated the highest antitumor potency. Moreover, VF3-transduced T cells mediated the efficient killing of HLA-A24+/SAGE1+ tumor cells in vitro and effectively inhibited the growth of lung cancer xenografts in mice. Together, our data suggest that SAGE1 could be a target for T-cell immunotherapies against lung cancer, while its specific TCRs could be candidates for developing reagents to treat SAGE1+ tumors.
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