Related Experiment Video
Updated: Oct 22, 2025
Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
SAGE1: a Potential Target Antigen for Lung Cancer T-Cell Immunotherapy
Yajing Zhang1,2, Xiaohong Yu3, Qiuping Liu3
1State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China.
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.
Insights
Sarcoma antigen 1 (SAGE1) is a promising target for lung cancer immunotherapy. Researchers identified a novel SAGE1 epitope and T-cell receptors that effectively target and inhibit SAGE1-positive lung tumors.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- T-cell immunotherapy efficacy relies on understanding cancer-specific antigens.
- Sarcoma antigen 1 (SAGE1), a cancer/testis antigen, lacks verification for T-cell immunotherapy.
- Non-small cell lung cancer (NSCLC) presents a significant therapeutic challenge.
Purpose of the Study:
- To investigate SAGE1 expression in NSCLC.
- To identify and characterize SAGE1-specific T-cell responses for potential immunotherapy.
- To evaluate the therapeutic potential of SAGE1-targeting T-cell receptors (TCRs).
Main Methods:
- Quantitative analysis of SAGE1 RNA expression.
- Immunohistochemistry (IHC) for SAGE1 protein detection in NSCLC tissues.
- Mass spectrometry to identify HLA-A*24:02-restricted SAGE1 epitopes.
- Isolation and characterization of SAGE1-specific T-cell clones and TCRs.
- In vitro and in vivo efficacy studies using engineered T cells.
Main Results:
- SAGE1 expression was detected in 50% of NSCLC samples (n=40).
- A novel HLA-A24-restricted SAGE1 epitope (SAGE1597-606, VFSTAPPAFI) was identified.
- High-affinity TCRs, particularly VF3, demonstrated potent antitumor activity.
- VF3-transduced T cells effectively killed SAGE1+/HLA-A24+ tumor cells in vitro and inhibited tumor growth in vivo.
Conclusions:
- SAGE1 is a viable target for T-cell immunotherapy in lung cancer.
- SAGE1-specific TCRs, like VF3, are promising candidates for developing novel cancer treatments.
- This study provides a foundation for SAGE1-based therapeutic strategies against SAGE1-expressing tumors.
More Related Videos
10:21Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
Published on: September 20, 2024
10:29Semi-automatic PD-L1 Characterization and Enumeration of Circulating Tumor Cells from Non-small Cell Lung Cancer Patients by Immunofluorescence
Published on: August 14, 2019
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:27Tumor Immunotherapy