The Tübingen approach: identification, selection, and validation of tumor-associated HLA peptides for cancer therapy.
There is substantial need for molecularly defined tumor antigens to prime cytotoxic T cells in vivo for cancer immunotherapy, especially in the case of tumor entities for which only a few tumor antigens have been defined so far. In this review, we present the "Tübingen approach" to identify, select, and validate large numbers of MHC/HLA class I-associated peptides derived from tumor-associated antigens. Step 1 is the identification of naturally presented HLA-associated peptides directly from primary tumor cells. Step 2 is selection of tumor-associated peptides from step 1 by differential gene expression analysis and data mining. Step 3 is validation of selected candidates by monitoring in vivo T-cell responses in the context of patient-individualized immunizations. Our approach combines methods from genomics, proteomics, bioinformatics, and T-cell immunology. The aim is to develop effective immunotherapeutics consisting of multiple tumor-associated epitopes in order to induce a broad and specific immune response against cancer cells.
Singh-Jasuja
Harpreet
H
Department of Immunology, Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany.
Emmerich
Niels P N
NP
Rammensee
Hans-Georg
HG
D000951:Antigens, Neoplasm / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D023281:Genomics; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I