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The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Identification of target antigens in specific immunotherapy for renal cell carcinoma
Yoshihiro Komohara1, Mamoru Harada, Yoshimi Arima
1Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Kurume University, Fukuoka, Japan.
Purpose:
Effective immunotherapy against renal cell carcinoma has not yet been established despite recent advances in specific immunotherapy for various malignancies. A plausible reason is limited information about target antigens of renal cell carcinoma. We searched for useful cancer antigens applicable to immunotherapy for renal cell carcinoma by examining antigen expression in renal cell carcinoma cell lines and testing the ability to induce renal cell carcinoma reactive cytotoxic T lymphocytes.
Materials And Methods:
mRNA expression of a panel of cancer associated antigens was examined using 5 renal cell carcinoma cell lines. Thereafter antigen derived peptides reported to induce cancer reactive cytotoxic T lymphocytes from human leukocyte antigen-A24+ patients with cancer were examined for their potential to induce cytotoxic T lymphocytes from peripheral blood mononuclear cells of human leukocyte antigen-A24+ patients with renal cell carcinoma.
Results:
Three candidate antigens, including multidrug resistance-associated protein 3, polycomb group protein enhancer of zeste homologue 2 and Her2/neu, were expressed in all 5 renal cell carcinoma cell lines. Six peptides derived from these antigens, including multidrug resistance-associated protein 3(503-511), multidrug resistance-associated protein 3(1293-1302), polycomb group protein enhancer of zeste homologue 2(291-299), polycomb group protein enhancer of zeste homologue 2(735-743), Her2/neu342-350 and Her2/neu485-493, efficiently induced peptide specific and renal cell carcinoma reactive cytotoxic T lymphocytes from human leukocyte antigen-A24+ patients with renal cell carcinoma. Blocking and cold inhibition assays revealed that cytotoxicity against renal cell carcinoma depended on human leukocyte antigen class I restricted and peptide specific CD8+ T cells.
Conclusions:
This information could facilitate the development of effective immunotherapy against renal cell carcinoma.
Insights
Researchers identified three key antigens (multidrug resistance-associated protein 3, enhancer of zeste homologue 2, and Her2/neu) expressed in renal cell carcinoma. Peptides from these antigens effectively stimulated cancer-fighting T cells, paving the way for new immunotherapies.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Effective immunotherapy for renal cell carcinoma (RCC) remains a challenge, potentially due to limited knowledge of target antigens.
- Recent advancements in cancer immunotherapy for other malignancies highlight the need for specific targets in RCC.
Purpose of the Study:
- To identify novel target antigens for renal cell carcinoma (RCC) immunotherapy.
- To evaluate the potential of identified antigens to induce RCC-specific cytotoxic T lymphocytes (CTLs).
Main Methods:
- Examined mRNA expression of cancer-associated antigens in five RCC cell lines.
- Assessed the ability of antigen-derived peptides to induce CTLs from peripheral blood mononuclear cells of HLA-A24+ RCC patients.
Main Results:
- Three antigens—multidrug resistance-associated protein 3 (MRP3), polycomb group protein enhancer of zeste homologue 2 (EZH2), and Her2/neu—were expressed in all tested RCC cell lines.
- Six peptides from MRP3, EZH2, and Her2/neu successfully induced peptide-specific and RCC-reactive CTLs in HLA-A24+ patients.
- Cytotoxicity was mediated by human leukocyte antigen class I-restricted and peptide-specific CD8+ T cells.
Conclusions:
- Identified promising target antigens and peptides for potential RCC immunotherapy.
- Findings support the development of novel immunotherapeutic strategies for renal cell carcinoma.
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