Integrated functional genomics approach for the design of patient-individual antitumor vaccines.
Our aim is to identify as many candidates as possible for tumor-associated T-cell epitopes in individual patients. First, we performed expression profiling of tumor and normal tissue to identify genes exclusively expressed or overexpressed in the tumor sample. Then, using mass spectrometry, we characterized up to 77 different MHC ligands from the same tumor sample. Several of the MHC ligands were derived from overexpressed gene products, one was derived from a proto-oncogene, and another was derived from a frameshift mutation. At least one was identified as an actual T-cell epitope. Thus, we could show that by combining these two analytic tools, it is possible to propose several candidates for peptide-based immunotherapy. We envision the use of this novel integrated functional genomics approach for the design of antitumor vaccines tailored to suit the needs of each patient.
Weinschenk
Toni
T
Department of Immunology, Institute for Cell Biology, University of Tübingen, Germany.
Gouttefangeas
Cécile
C
Schirle
Markus
M
Obermayr
Florian
F
Walter
Steffen
S
Schoor
Oliver
O
Kurek
Raffael
R
Loeser
Wolfgang
W
Bichler
Karl-Horst
KH
Wernet
Dorothee
D
Stevanović
Stefan
S
Rammensee
Hans-Georg
HG
D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D016368:Frameshift Mutation; D020869:Gene Expression Profiling; D015234:HLA-A Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D015235:HLA-B Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007633:Keratins / Q000276:immunology; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D008565:Membrane Proteins; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000070780:Perilipin-2; D000090063:Proto-Oncogene Mas
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015235:HLA-B Antigens; C000715470:MAS1 protein, human; D008565:Membrane Proteins; D010455:Peptides; D000070780:Perilipin-2; D000090063:Proto-Oncogene Mas; D007633:Keratins