Commissariat &#xc0; L'&#xc9;nergie Atomique Et Aux &#xc9;nergies Alternatives

Commissariat a L'energie Atomique

Assistance Publique-hopitaux De Paris

Etablissement Francais Du Sang

Hla-g Technologies

Nathalie Rouas-Freiss

Edgardo Delfino Carosella

Jean Dausset

Pascale Paul

Jean-Philippe Deslys

Marek Kirszenbaum

François Desgrandchamps

Philippe Moreau

Luc Sensebe

Jérôme Verine

Diana Tronik-Le Roux

Joël Le Maoult

Abderrahim Naji

Embodiments of the disclosure pertain to the field of HLA-G molecules and their therapeutic use. The disclosure pertains to new HLA-G isoforms, that is to say new RNA transcripts and proteins deriving from the HLA-G gene, pharmaceutical composition comprising thereof, as well as primers specific of these transcripts and antibodies specific of these proteins. The disclosure further pertains to the diagnostic or therapeutic use of these molecules.

HLA-G transcripts and isoforms and their uses

Novel use of HLA-G isoforms in the treatment or prevention of diseases in which bone resorption is observed.

HLA-G isoform for use in the treatment of a disease associated with bone resorption

The invention concerns a method for selecting tumours expressing HLA-G, sensitive to an anticancer treatment, which inhibits or prevents the HLA-G activity of said tumours and the uses thereof. Said method enable to establish either the HLA-G, transcription profile of a solid tumour or the HLA-G expression profile of a solid tumour. The method for establishing the HLA-G transcription profile consists in: (i) drawing a tumoral sample; (ii) extracting the mRNA; (iii) reverse transcription (RT) of said RNA: (iv) successive or simultaneous amplification of the cDNA's obtained in (iii) in the presence of primers specific to each HLA-G isoform and analysing the resulting amplification products, by electrophoresis and/or specific hybridisation and (v) establishing said sample HLA-G transcription profile. The method for establishing the HLA-G expression profile consists in: (i) drawing a tumoral sample; (ii) optionally marking said sample cells; (iii) carrying out a lysis of the cells; (iv) contacting said cells which have been subjected to lysis with different antibodies directed against the class I HLA-G antigens, to form, optionally HLA-G isform/antibodies complexes; and (v) establishing said sample HLA-G expression profile by detecting the complexes formed in step (iv).

Method for selecting tumours expressing HLA-G, sensitive to anticancer treatment and uses

The invention concerns the use of a eukaryotic cell coding for at least an HLA-G isoform, to obtain an immunomodulating medicine for inhibiting the activity of killer cells, in particular NK cells and/or for inhibiting the primary allogenic response, in parthologies or situations in which the killer cells are activated or for preparing a medicine to raise the inhibiting function of the isoform(s) expressed by said cells with respect to killer cells, in particular NK cells, in pathologies where these killer cells are inhibited by the molecule of the major histocompatibility complex of I HLA-G classes. The invention also concerns eukaryotic cells expressing at their surface at least an HLA-G isoform and their applications. The invention further concerns transgenic animals specifically expressing at least an HLA-G isoform.

Eukaryotic cells expressing at their surface at least an HLA-G isoform and their applications

Growing community of inventors

Paris, France

Nathalie Rouas-Freiss