Provided are methods, polynucleotides and compositions for the generation of engineered Treg cells. The methods, polynucleotides and compositions enable the reprogramming of hematopoietic cells into Treg cells by constitutive or regulated expression of FOXP3 in engineered cells such that the engineered Treg cells can suppress the activation and proliferation of responder T cells.

The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

The present invention provides a mutated woodchuck post-transcriptional regulatory element (WPRE). In particular, the present invention relates to a mutated WPRE sequence that can efficiently express nucleotides of interest in a retroviral vector system. The present invention also relates to methods of delivering and expressing nucleotides of interest to a target cell.

A method of preparing an allogenic dendritic stem cell vaccine for treating ovarian cancers is disclosed. The method comprises, (a) collecting blood sample from an allogenic donor in a sterile collection bag, (b) separating viable mesenchymal stem cells inoculums by centrifuging the blood sample, suspending said mesenchymal stem cells inoculum in proliferation medium, plating the cells in a flask and incubated, and collecting cells adherent to the flask and further harvesting and expanding said adherent cells, (c) preparing myeloid dendritic cells by isolating, harvesting and culturing said blood sample source using myeloid dendritic isolation kit, (d) mixing the adherent cells obtained. Finally, (e) the composition of the adherent cells obtained in step (d) to the myeloid dendritic cells obtained in step (c) at a ratio of 90:10 and printing the cellular vectors with patient tumor derived heterogeneous progenitors.

A method of generating an isolated population of cells comprising anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance-inducing cells and/or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) contacting peripheral blood mononuclear cells (PBMC) with a third party antigen or antigens in the presence of IL-21 so as to allow enrichment of antigen reactive cells; and (b) culturing the cells resulting from step (a) in the presence of IL-21, IL-15 and IL-7 in an antigen free environment so as to allow proliferation of cells comprising the central memory T-lymphocyte (Tcm) phenotype.

Disclosed is a method for obtaining a population of human Treg cells including the steps of: (a) culturing a population of human monocytes with a medium including an amount of an interleukin-34 (IL-34) polypeptide in order to obtain a population of immunosuppressive macrophages; (b) co-culturing a population of human peripheral blood mononuclear cells (PBMCs) and the population of immunosuppressive macrophages obtained at step (a).

The present invention discloses selective surfaces, wherein said selective surfaces comprise a biocompatible polymer comprising maleic anhydride molecules and an apoptosis inducing ligand bound to the maleic anhydride molecules. The invention also encompasses devices and kits comprising the selective surface and methods for its production. The selective surfaces may be used for functional selection of cell populations suitable for transplantation into human subjects.

Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

The invention provides compositions and methods for treating diseases associated with expression of CD19, e.g., by administering a recombinant T cell comprising the CD19 CAR as described herein, in combination with a BTK inhibitor, e.g., an amino pyrimidine derivative described herein. The invention also provides kits and compositions described herein.