[Application of molecular modeling to new therapeutic cancer approaches].
Recent progress in the experimental determination of protein structures allow to understand, at a very detailed level, the molecular recognition mechanisms that are at the basis of the living matter. This level of understanding makes it possible to design rational therapeutic approaches, in which effectors molecules are adapted or created de novo to perform a given function. An example of such an approach is drug design, were small inhibitory molecules are designed using in silico simulations and tested in vitro. In this article, we present a similar approach to rationally optimize the sequence of killer T lymphocytes receptors to make them more efficient against melanoma cells. The architecture of this translational research project is presented together with its implications both at the level of basic research as well as in the clinics.
Michielin
Olivier
O
Centre du cancer de Lausanne, Lausanne. olivier.michielin@unil.ch
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000951:Antigens, Neoplasm / Q000276:immunology; D003198:Computer Simulation; D017124:Conserved Sequence; D006801:Humans; D016219:Immunotherapy, Adoptive; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008565:Membrane Proteins / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D025941:Protein Interaction Mapping; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D037182:T-Cell Antigen Receptor Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology*
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell