Lessons to be learned from primary renal cell carcinomas: novel tumor antigens and HLA ligands for immunotherapy.
The lack of sufficient well-defined tumor-associated antigens is still a drawback on the way to a cytotoxic T-lymphocyte-based immunotherapy of renal cell carcinoma (RCC). We are trying to define a larger number of such targets by a combined approach involving HLA ligand characterization by mass spectrometry and gene expression profiling by oligonucleotide microarrays. Here, we present the results of a large-scale analysis of 13 RCC specimens. We were able to identify more than 700 peptides, mostly from self-proteins without any evident tumor association. However, some HLA ligands derived from previously known tumor antigens in RCC. In addition, gene expression profiling of tumors and a set of healthy tissues revealed novel candidate RCC-associated antigens. For several of them, we were able to characterize HLA ligands after extraction from the tumor tissue. Apart from universal RCC antigens, some proteins seem to be appropriate candidates in individual patients only. This underlines the advantage of a personalized therapeutic approach. Further analyses will contribute additional HLA ligands to this repertoire of universal as well as patient-individual tumor antigens.
Krüger
Tobias
T
Department of Immunology, Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany.
Schoor
Oliver
O
Lemmel
Claudia
C
Kraemer
Bjoern
B
Reichle
Christian
C
Dengjel
Jörn
J
Weinschenk
Toni
T
Müller
Margret
M
Hennenlotter
Jörg
J
Stenzl
Arnulf
A
Rammensee
Hans-Georg
HG
Stevanović
Stefan
S
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000032:analysis*; D021241:Spectrometry, Mass, Electrospray Ionization; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D006680:HLA Antigens; D008024:Ligands; D010446:Peptide Fragments