Method of strengthening foreign epitope presentation by mhc...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/63 (2006.01) C07K 14/16 (2006.01) C07K 14/74 (2006.01) C07K 19/00 (2006.01) C12N 5/10 (2006.01) C12N 15/12 (2006.01) C12N 15/62 (2006.01) C12N 15/67 (2006.01)

Patent

CA 2500413

A method of strengthening the presentation of a foreign epitope by MHC class I by inhibiting TAP activity. A mammalian cell-infecting viral vector encoding both of a TAP inhibitor and epitope-binding .beta.2m is constructed and transferred into mammalian cells. Thus, endogenous MHC class I/peptide complexes are decreased by the TAP inhibitor and MHC class I/peptide complexes containing epitope-binding .beta.2m expressed from the vector are successfully presented on the cell surface at a high frequency. This method is useful in the vaccine therapy for infection and cancer.

La présente invention concerne un procédé permettant, par inhibition de l'activité TAP, de renforcer la présentation d'épitopes étrangers par les MHC de classe I. En l'occurrence, on construit un vecteur viral infectant les cellules de mammifères, et codant aussi bien un inhibiteur TAP qu'un .beta.2m se liant aux épitopes, et on le transfère dans des cellules de mammifères. Ainsi, d'une part l'inhibiteur TAP fait diminuer les complexes formés entre MHC endogènes de classe I et peptides, et d'autre part les complexes entre MHC de classe I et peptides, qui contiennent un .beta.2m de liant à un épitope et exprimés à partir du vecteur, se présentent avec succès à la surface de la cellule à une fréquence élevée. Ce procédé convient en thérapie vaccinale dirigée contre les infections et les cancers.

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