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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Simultaneous expression of T-cell activating antigens in renal cell carcinoma: implications for specific
Mark Ringhoffer1, Carlheinz R Müller, Ariane Schenk
1Departments of Internal Medicine III, University Hospital and German National Bone Marrow Donor Registry, Ulm, Germany.
Purpose:
The activation of antigen specific T cells by tumor associated antigens (TAA) might be a promising treatment strategy for patients with renal cell carcinoma (RCC). We analyzed TAA expression in patients with RCC as well as the prevalence of fitting HLA phenotypes and calculated the percent of patients eligible for peptide vaccination trials.
Materials And Methods:
A total of 41 RCC samples from primary tumors were analyzed for TAA expression by reverse transcriptase-polymerase chain reaction. Genes of interest were MAGE-1, MAGE-3, G250 and PRAME since peptides derived from these genes have been shown to activate antigen specific cytotoxic T lymphocytes. Results were combined with data on the HLA gene and haplotype frequencies in the German population as an example of a white population.
Results:
Tumor specific expression of at least 1 T-cell activating antigen was observed in all patients. Of the patients 80% expressed 2 or more TAAs simultaneously. HLA molecules suitable for presentation of the respective antigens were calculated to be expressed in 51% to 85% of white German patients. These results mirror with only minor variations most of the white populations in Europe and North America.
Conclusions:
We noted that T-cell activating tumor associated antigens are frequently expressed in patients with RCC. Based on HLA expression analysis in a white population at least 30% of patients with RCC are eligible for monovalent specific immunotherapy and 41% are eligible for polyvalent specific immunotherapy. These data are a rational basis for future prospective vaccination trials in patients with RCC.
Insights
Tumor-associated antigens (TAAs) are frequently expressed in renal cell carcinoma (RCC) patients. Many patients are eligible for specific immunotherapy trials based on antigen and HLA expression.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Tumor-associated antigens (TAAs) hold promise for targeted therapies in renal cell carcinoma (RCC).
- Activation of antigen-specific T cells is a potential treatment strategy for RCC.
- Understanding TAA expression and HLA phenotypes is crucial for patient eligibility in immunotherapy trials.
Purpose of the Study:
- To analyze TAA expression in RCC patient samples.
- To determine the prevalence of suitable HLA phenotypes in the German population.
- To calculate the percentage of RCC patients eligible for peptide vaccination trials.
Main Methods:
- Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyze TAA expression (MAGE-1, MAGE-3, G250, PRAME) in 41 primary RCC tumors.
- TAA expression data were combined with HLA gene and haplotype frequencies in the German population.
- Eligibility for peptide vaccination trials was calculated based on antigen and HLA expression.
Main Results:
- All analyzed RCC patients expressed at least one T-cell activating antigen.
- 80% of patients simultaneously expressed two or more TAAs.
- HLA molecules for antigen presentation were found in 51% to 85% of white German patients, mirroring other white populations.
Conclusions:
- T-cell activating TAAs are frequently expressed in RCC patients.
- Based on HLA analysis, 30% of RCC patients are eligible for monovalent and 41% for polyvalent specific immunotherapy.
- These findings provide a rationale for prospective peptide vaccination trials in RCC.
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