Antibodies as t cell receptor mimics, methods of production...

A - Human Necessities – 61 – K

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Details

A61K 39/00 (2006.01) C07H 21/04 (2006.01) C12N 5/12 (2006.01) C12N 5/18 (2006.01) C12P 21/08 (2006.01)

Patent

CA 2567814

The present invention relates to a methodology of producing antibodies that recognize peptides associated with a tumorigenic or disease state, wherein the peptides are displayed in the context of HLA molecules. These antibodies will mimic the specificity of a T cell receptor (TCR) but will have higher binding affinity such that the molecules may be used as therapeutic, diagnostic and research reagents. The method of producing a T-cell receptor mimic of the present invention includes identifying a peptide of interest, wherein the peptide of interest is capable of being presented by an MHC molecule. Then, an immunogen comprising at least one peptide/MHC complex is formed, wherein the peptide of the peptide/MHC complex is the peptide of interest. An effective amount of the immunogen is then administered to a host for eliciting an immune response, and serum collected from the host is assayed to determine if desired antibodies that recognize a three-dimensional presentation of the peptide in the binding groove of the MHC molecule are being produced. The desired antibodies can differentiate the peptide/MHC complex from the MHC molecule alone, the peptide alone, and a complex of MHC and irrelevant peptide. Finally, the desired antibodies are isolated.

L'invention porte sur un procédé de production d'anticorps reconnaissant les peptides associés à des états tumorogènes ou morbides et se présentant dans un contexte de molécules HLA. Lesdits anticorps, qui miment la spécificité d'un récepteur de cellule T (TCR), ont toutefois une plus grande affinité, ce qui permet d'utiliser les molécules comme réactifs thérapeutiques, diagnostiques et de recherche. Le procédé d'obtention de ces mimétiques de récepteurs de cellules T consiste: à identifier un peptide d'intérêt pouvant être présenté par une molécule de CMH; puis à former un immunogène comprenant au moins un complexe peptide/CMH dont le peptide est le peptide d'intérêt; puis à administrer une quantité efficace de l'immunogène à un hôte pour susciter une réponse immunitaire; puis à essayer un sérum provenant de l'hôte pour déterminer si les anticorps désirés qui reconnaissent la présentation en 3 D du peptide dans le sillon de fixation de la molécule de CMH ont été formés, les anticorps désirés pouvant différencier le complexe peptide/CMH de la molécule de CMH seule, du peptide seul et d'un complexe peptide/CMH ou d'un peptide non pertinents; puis à isoler les anticorps désirés.

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