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Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular
Kiichiro Kaji1, Eishiro Mizukoshi1, Tatsuya Yamashita1
1Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan.
Background & Aims:
Squamous cell carcinoma antigen recognized by T cells 3 (SART3), a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC).
Methods:
The expression of SART3 in hepatoma cell lines and HCC tissues was investigated by immunofluorescence and immunohistochemical analyses. Two peptides derived from SART3 (SART3109 and SART3315) were used for immunological analysis. T-cell responses were investigated by interferon-gamma (IFN-γ) enzyme-linked immunospot and cytotoxic T lymphocyte (CTL) assays using peripheral blood mononuclear cells (PBMCs) in 47 patients, and tumor-infiltrating lymphocytes in 8 of 47 patients with HCC. The safety of immunotherapy using a SART3-derived peptide was investigated by vaccinations of SART3109 in 12 patients with HCC (trial registration: UMIN000005677).
Results:
The immunofluorescence and immunohistochemical analyses showed that SART3 was expressed in six HCC cell lines, and in HCC tissues including of alpha-fetoprotein-negative individuals. SART3-specific CTLs were generated by stimulating PBMCs with the peptides, and they showed cytotoxicity against HCC cells expressing the protein. Of the 47 HCC patients, 25.5% and 10.6% showed significant responses to SART3109 and SART3315, respectively. The infiltration of SART3109-specific IFN-γ-producing CTLs into the tumor site was confirmed. In the vaccination study, no severe adverse events were observed, and the peptide-specific CTLs were newly induced in four of five patients tested.
Conclusions:
SART3 is an immunotherapeutic candidate, and peptides from this antigen may be applied in HCC immunotherapy.
Trial Registration:
UMIN000005677.
Insights
Squamous cell carcinoma antigen recognized by T cells 3 (SART3) shows promise for hepatocellular carcinoma (HCC) immunotherapy. SART3-specific T-cell responses were observed, and peptide vaccination was safe and effective in inducing immune responses in HCC patients.
Area of Science:
- Immunology
- Oncology
- Cancer Immunotherapy
Background:
- Squamous cell carcinoma antigen recognized by T cells 3 (SART3) is a tumor-associated antigen involved in tumor rejection.
- SART3 expression is observed in various cancers, making it a potential target for cancer immunotherapy.
- Hepatocellular carcinoma (HCC) is a significant global health concern with limited effective immunotherapeutic options.
Purpose of the Study:
- To investigate the potential of SART3 as an immunotherapeutic target in hepatocellular carcinoma (HCC).
- To evaluate T-cell responses against SART3-derived peptides in HCC patients.
- To assess the safety and immunogenicity of SART3-based peptide vaccination in HCC.
Main Methods:
- SART3 expression was analyzed in HCC cell lines and tissues using immunofluorescence and immunohistochemistry.
- T-cell responses were assessed using interferon-gamma (IFN-γ) enzyme-linked immunospot and cytotoxic T lymphocyte (CTL) assays with SART3-derived peptides (SART3109, SART3315).
- A Phase I vaccination trial using SART3109 peptide was conducted to evaluate safety and immune induction in HCC patients.
Main Results:
- SART3 was expressed in HCC cell lines and tissues, including in alpha-fetoprotein-negative HCC.
- SART3-specific CTLs were generated and demonstrated cytotoxicity against HCC cells.
- Peptide vaccination induced SART3-specific CTLs in a majority of vaccinated patients with no severe adverse events.
Conclusions:
- SART3 is a viable immunotherapeutic target for hepatocellular carcinoma.
- Peptides derived from SART3 hold potential for application in HCC immunotherapy.
- SART3-based peptide vaccination is a safe and immunogenic approach for HCC treatment.
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