Commissariat a L'energie Atomique

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

Institut Pasteur

Institut National De La Recherche Agronomique (inra)

Hla-g Technologies

Marek Kirszenbaum

Edgardo Delfino Carosella

Philippe Moreau

Stéphane Prost

Eliane Gluckman

Philippe Leboulch

Nathalie Rouas-Freiss

Jean Dausset

Marc Fellous

Pascale Paul

Magali Le Discorde

Philippe Rousselot

Mikael Le Dantec

Corinne Cotinot

Marcel Vaiman

Colin Bishop

Philipe Leboulch

Provided are methods for eliminating hematologic cancer stem cells in vivo, and thus preventing cancer relapse. The methods comprise a Signal Transducer and Activator of Transcription 5 (STAT5) antagonist (e.g., a PPAR&#x3b3; agonist) after the patient has had ana initial course of treatment with an anti-cancer agent (e.g., a TKI), to eliminate residual cancer stem cells which cause relapse.

Combination of an anti-cancer agent such as a tyrosinekinase inhibitor and a STAT5 antagonist, preferably a thiazolidinedione, for eliminating hematologic cancer stem cells in vivo and for preventing hematologic cancer relapse

The invention concerns a protein present at the surface of hematopoietic stem cells of the lymphoid cell line and mature NK cells, the corresponding isolated cDNA sequence and their uses as marker of said cells and for preparing antibodies directed against said protein. The invention also concerns the uses of said antibodies for selecting cells expressing at their surface said protein. Said isolated protein has a structure (a) comprising an extracellular domain located between positions 21 and 152, five transmembrane domains located between positions 153 and 295 and a cytoplasmic domain located between positions 296 and 350, with reference to the sequence SEQ ID NO:2; an apparent molecular weight of about 36 to 38 kDa, and its precursor, which comprises in N-terminal of structure (a), a signal sequence of 20 amino acids, is selected in the group consisting of the protein of SEQ ID NO:2, and the proteins having an amino acid sequence having at least 70% identity or at least 85% similarity and preferably at least 95% identity or at least 99% similarity with the sequence SEQ ID NO:2.

Isolated mammalian protein present at the surface of all lymphoid progenitor cells and all mature NK cells and uses thereof

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

Transcripts of the major histocompatibility complex (MHC) Class I HLA-G gene which are present in foetal trophoblasts and/or in adult circulating mono-nuclear cells, as well as their applications. Either the said transcripts comprise, in succession in the 5&prime; to 3&prime; direction: a fragment encoding the signal peptide (exon 1), a fragment encoding the &agr;1 domain (exon 2), a fragment encoding the &agr;2 domain (exon 3), a fragment encoding the transmembrane TM domain (exon 5), a fragment encoding the cytoplasmic domain (exon 6) and the 3&prime; untranslated fragment (exon 8), which sequence is designated HLA-G4, or the said transcripts comprise intron 4.

Transcripts of the MHC class I HLA-G gene and their applications

Transcripts of the major histocompatibility complex (MHC) Class I HLA-G gene which are present in foetal trophoblasts and/or in adult circulating mono-nuclear cells, as well as methods of using these. Either the said transcripts comprise, in succession in the 5' to 3' direction: a fragment encoding the signal peptide (exon 1), a fragment encoding the .alpha.1 domain (exon 2), a fragment encoding the .alpha.2 domain (exon 3), a fragment encoding the transmembrane TM domain (exon 5), a fragment encoding the cytoplasmic domain (exon 6) and the 3' untranslated fragment (exon 8), which sequence is designated HLA-G4, or the said transcripts comprise intron 4.

Synthetic oligonucleotides of 17 or more consecutive nucleotides of the 49 bases of formula (A) to be used as molecular probes for sexing the embryos or foetuses of ruminant mammals or as molecular probes for detecting a Y chromosome in a spermatozoid population of ruminant mammals of the Bos genus and their use in process of amplification and hybridization assays.

Specific DNA molecular probes for Bos-type male genome

Growing community of inventors

Paris, France

Marek Kirszenbaum