Methods, compositions and kits for producing functional antigen-specific regulatory T cells (Tr1 cells) by reprogramming non-Tr1 target cells with suitable transcription factors.

The present disclosure provides a population of polydonor CD4.sup.IL-10 cells generated by genetically modifying CD4.sup.+ T cells from at least two different T cell donors. Further provided are methods of generating the polydonor CD4.sup.IL-10 cells and methods of using the polydonor CD4.sup.IL-10 cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, autoimmune and inflammatory diseases and other immune disorders.

The present invention relates to regulatory T cell and uses thereof. By their immunosuppressive and anti-inflammatory activities, regulatory T cells play a central role in peripheral tolerance and thus critically prevent the development of autoimmune and inflammatory disorders. The inventors showed that Foxp3+CD4+ Tregs express high levels of LT, which negatively regulates their immunosuppressive signature. They demonstrated that the adoptive transfer of LT/ Tregs in mice protects from dextran sodium sulfate (DSS)-induced colitis and attenuates inflammatory bowel disease (IBD), multi-organ autoimmunity and the development of CAC. The inventors also showed that by mixed bone marrow chimeras that LT expression specifically in hematopoietic cells negatively controls the immunosuppressive signature of Tregs. In particular, the present invention relates to regulatory T cell characterized in that it does not express or expresses reduced levels of lymphotoxin alpha.

A method of treating an inflammatory disorder in a subject, comprising administering to a subject in need thereof a nucleic acid molecule for inhibiting the expression of Hom-1.

The present disclosure relates to combination therapy compositions and methods comprising chimeric Tim receptors, host cells modified to include chimeric Tim receptor molecules, and PARP inhibitors.

The present disclosure features allogeneic modified cells (e.g., T- or NK-cells) having increased persistence, increased resistance to immune rejection, or decreased risk of eliciting a host-versus-graft reaction, or a combination thereof. Methods for producing and using the same are also provided.

Some embodiments of the methods and compositions provided herein relate to efficient editing of more than one genetic locus in a cell using a chemical-inducible signaling complex (CISC) system. Some embodiments include use of such systems to edit a FOXP3 locus gene and TRAC locus in a Treg cell. More embodiments herein relate to use of gene-edited Treg cells to suppress activation and/or proliferation of certain populations of cells.

Disclosed herein are exogenous antigen sensitized immature dendritic cells. The dendritic cell may also be dead. The exogenous antigen sensitized immature dendritic cells may be used to elicit an increased immune response. Further provided are vaccines comprising the exogenous antigen sensitized immature dendritic cells, methods, of inducing an immune response in a patient, and methods of treating a disease.

This disclosure describes production of hybrid peptides, including hybrid insulin peptides (HIPs), by antigen presenting cells (APCs).

The present invention relates to the use of immunoregulatory macrophages for treating diseases that are associated with pathological changes of the blood vessels. The present invention particularly relates to the use of immunoregulatory macrophages for treating micro- and macroangiopathies of the lower limbs. The invention furthermore relates to the use of immunoregulatory macrophages for promoting tissue remodelling to facilitate wound healing. Pharmaceutical compositions for use in the recited treatments are also disclosed which comprise the immunoregulatory macrophages.