Simultaneous expression of T-cell activating antigens in renal cell carcinoma: implications for specific immunotherapy.
OBJECTIVE
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.


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.
Ringhoffer
Mark
M
Departments of Internal Medicine III, University Hospital and German National Bone Marrow Donor Registry, Ulm, Germany.
Müller
Carlheinz R
CR
Schenk
Ariane
A
Kirsche
Hanspeter
H
Schmitt
Michael
M
Greiner
Jochen
J
Gschwend
Jürgen E
JE
D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D000945:Antigens, Differentiation, T-Lymphocyte