13 février 2014: Hans-Georg Rammensee
Thursday, February 13th 2014, 12h30
Pr Dr Hans-Georg Rammensee
Department of Immunology, University of Tübingen, Germany
Peptide-Based Immunotherapy of Cancer
Essentially all of our cells express surface molecules (HLA) that perform a kind of “real time analysis of the functional genome”: Samples of peptides representing all gene products expressed by a cell are presented by HLA molecules. This allows our T cells to sense the integrity of cells. Alterations, including mutations intrinsic to tumor cells, can thus be sensed by T cells. Each individual tumor expresses its own set of mutations (dozens to hundreds), some being essential for tumor growth, others being passenger mutations. Both categories can give rise to immunogenic peptides recognizable by T cells that can kill the tumor cells. In addition, tumor cells show overexpression of several gene products which can give rise to correspondingly higher density of the respective HLA-presented peptides that again can be sensed by T cells. Thus, we are confronted with two layers of individuality: Each human being has his or her own set of HLA molecules, with individual peptide specificities, and each tumor owns its individually accumulated set of mutations and overexpression of genes. It is possible to find peptides representing overexpressed gene products shared by cancer patients expressing a particular HLA-allel, such as HLA-A2. Such peptides have been used for immunotherapy of cancer with some success. The ultimate consequence for immunotherapy of cancer, however, is an individualized approach: Identify the mutations/alterations in the tumor, identify the new peptides presented on the tumor’s HLA, synthesize these peptides, for each patient individually, and vaccinate the very same patient with these peptides, using appropriate adjuvants and conditions. The feasibility as well as the challenges of this strategy will be discussed.