The invention is in the field of medical sciences. It provides means and methods for the treatment of cancer. More in particular, it provides cells and cell lines that can be developed into fully functional dendritic cells. These cells endogenously express cancer-specific antigens, which makes them particularly suited for the treatment of different kinds of cancer. More in particular, the invention relates to a precursor cell line for dendritic cells called DC-One as deposited at the DSMZ under accession number DSMZ ACC3189 on Nov. 15, 2012.

Natural Treg (nTreg) can potentially suppress cell immune response. Consequently, these CD4+ CD25+ CD127low Foxp3+ T cells are used in adoptive therapy against autoimmune and GVH disease. One difficulty is the varying functional properties depending on the microenvironment that may cause the loss of their suppressive activity and promote TH17- induced inflammatory effects. By ex vivo transdetermination of CD31 TH0 cells, the inventors established and expanded a Foxp3 regulatory T cell population (CD31d-Treg cells) functionally committed to exert a permanent Ag-specific regulatory activity whichever the microenvironmental conditions are. By contrast to nTreg cells, CD31d-Treg cells do not express the IL1 Receptor whose activation is required for IL-17 production. Accordingly, the present invention relates to a population of CD31d-Treg cells functionally committed to exert a regulatory activity and their use for Treg-based adoptive therapy.

The receptor EP.sub.4 is identified as the PGE.sub.2 receptor that is most responsible enhancing the homing and engraftment of hematopoietic stem and progenitor cells. Treatment of graft sources and graft recipients with compounds that preferentially target the EP.sub.4 receptor provide effective methods of increasing engraftment success while minimizing adverse side effects that may Obe associated with therapies that include the use of less selective molecules such as PGE.sub.2 and dmPGE.sub.2. One effective molecule used in such therapies is 5-[(1E,3R)-4,4-ditluoro-3-hydroxy-4-phenyl-1-buten-1-yl]-1-[6-(2H-tetrazol-5R-yl)hexyl]-2-pyrrolidinone or a pharmaceutically acceptable salt thereof (L-902, 685).

The present invention relates to an in vitro culture of haematopoietic cells, wherein said haematopoietic cells differentiate to form granulocytes characterised by the ability to kill cancer cells. The invention also relates to said granulocytes, methods for identifying said haematopoietic cells and granulocytes, compositions and kits comprising the same, as well as uses of the same for treating cancer.

This disclosure is directed to the methods of enhancing hematopoietic stem cells (HSPC) and progenitor cell (HSPC) engraftment procedure. Treatment in vivo of a HSPC donor with compounds that reduce PGE.sub.2 biosynthesis or PGE.sub.2 receptor antagonists alone, or in combination with other hematopoietic mobilization agents such as AMD3100 and G-CSF, increases the circulation of available HSPCs. Compounds that reduce the cellular synthesis of PGE.sub.2 include non−steroidal anti-inflammatory compounds such as indomethacin. Treatment ex vivo of HSPC with an effective amount of PGE.sub.2 or at least one of its derivatives such as 16,16-dimethyl prostaglandin E.sub.2 (dmPGE.sub.2), promotes HSPC engraftment. Similar methods may also be used to increase viral-mediated gene transduction efficacy into HSPC.

The receptor EP.sub.4 is identified as the PGE.sub.2 receptor that is most responsible enhancing the homing and engraftment of hematopoietic stem and progenitor cells. Treatment of graft sources and graft recipients with compounds that preferentially target the EP.sub.4 receptor provide effective methods of increasing engraftment success while minimizing adverse side effects that may be associated with therapies that include the use of less selective molecules such as PGE.sub.2 and dmPGE.sub.2. One effective molecule used in such therapies is 5-[(1E,3R)-4,4-difluoro-3-hydroxy-4-phenyl-1-buten-1-yl]-1-[6-(2H-tetrazol-5R-yl)hexyl]-2-pyrrolidinone or a pharmaceutically acceptable salt thereof (L-902, 688).

Provided herein are compositions and methods for preparing T cell compositions and uses thereof, including methods for treating cancer in a subject in need thereof by administering T cells induced with peptides comprising an epitope sequence from a library of epitope sequences, wherein each epitope sequence in the library is matched to a protein encoded by an HLA allele and binds to a protein encoded by an HLA allele of the subject, is immunogenic according to an immunogenic assay, is presented by antigen presenting cells according to a mass spectrometry assay, and stimulates T cells to be cytotoxic according to a cytotoxicity assay.

The present invention provides methods and compositions for improving efficacy of viral transduction of cells. More particularly, the present invention provides methods and materials useful for safely and reliably improving the efficiency of methods and materials useful for safely and reliably improving the efficiency of methods for transducing cells, such as human hematopoietic stem cells (HSC), with viruses and/or viral vectors. The compositions and methods are useful for therapeutic indications amenable to treatment with hematopoietic stem cell gene therapies.

Provided are methods for treating or preventing vasculopathy in a subject in need thereof, comprising administering to the subject a prostacyclin and a mesenchymal stem cell (MSC) or a MSC-conditioned culture medium or administering to the subject a MSC or a MSC-conditioned culture medium that has treated with prostacyclin. Pharmaceutical compositions suitable for such treatments are also provided.

The invention relates to a method for inducing human cholangiocyte differentiation of progenitor cells called hepatoblasts. More specifically, the invention relates to a method for differentiating hepatoblasts to cholangiocytes by culturing said hepatoblasts with a particular medium having interleukin-6 (IL-6) activity. The differentiation method can specifically induce cholangiocyte dilferentiation from hepatoblasts, and the human cholangiocytes differentiated according to the invention may be useful for drug discovery for treatment of cholangiopathies and bioengineered livers.