Integrated functional genomics approach for the design of patient-individual antitumor vaccines

• Published in: Cancer research (Chicago, Ill.) Vol. 62; no. 20; pp. 5818 - 5827
• Main Authors: WEINSCHENK, Toni, GOUTTEFANGEAS, Cécile, STEVANOVIC, Stefan, RAMMENSEE, Hans-Georg, SCHIRLE, Markus, OBERMAYR, Florian, WALTER, Steffen, SCHOOR, Oliver, KUREK, Raffael, LOESER, Wolfgang, BICHLER, Karl-Horst, WERNET, Dorothee
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.10.2002
• Subjects: Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - genetics; Cancer Vaccines - immunology; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - therapy; CD8-Positive T-Lymphocytes - immunology; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Frameshift Mutation; Gene Expression Profiling; HLA-A Antigens - biosynthesis; HLA-A Antigens - genetics; HLA-A Antigens - immunology; HLA-B Antigens - biosynthesis; HLA-B Antigens - genetics; HLA-B Antigens - immunology; Humans; Immunotherapy; Keratins - immunology; Kidney Neoplasms - genetics; Kidney Neoplasms - immunology; Kidney Neoplasms - metabolism; Kidney Neoplasms - therapy; Medical sciences; Membrane Proteins; Oligonucleotide Array Sequence Analysis; Peptides - genetics; Peptides - immunology; Peptides - metabolism; Perilipin-2; Pharmacology. Drug treatments; Antineoplastic agent; Human; Cell recognition; Tumor associated antigen; Antigenic determinant; Genomics; Tumoral tissue; T-Lymphocyte; Gene overexpression; Vaccine; Malignant tumor; Gene expression
• ISSN: 0008-5472; 1538-7445

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.