Disclosed are means, methods and compositions of matter for treatment of Graves’ Disease using non-modified and/or modified fibroblasts for promotion of immunological tolerance, and/or stimulation of antigen-specific tolerance. In some embodiments, fibroblasts are administered together with antigens associated with Graves’ Disease such as the thyrotropin receptor protein and/or peptides and/or altered peptide ligands derived thereof. In some embodiments, co-administration refers to administration simultaneously or within temporal proximity of each other. In some embodiments, co-administration refers to loading of fibroblasts with antigens and/ or epitopes of antigens associated with Graves’ Disease.

The present disclosure provides methods for re-stimulating TIL populations that lead to improved phenotype and increased metabolic health of the TILs and provides methods of assaying for TIL populations to determine suitability for more efficacious infusion after re-stimulation.

The present disclosure provides methods for re-stimulating TIL populations that lead to improved phenotype and increased metabolic health of the TILs and provides methods of assaying for TIL populations to determine suitability for more efficacious infusion after re-stimulation.

A method of obtaining a pancreatic multipotent or unipotent cell including providing a cell of a first type which is not a pancreatic multipotent or unipotent cell; contacting the cell of a first type with an agent capable of remodeling the chromatin and/or DNA of the cell; transiently increasing expression of at least one pancreatic multipotent or unipotent gene regulator in the cell of a first type, to a level at which the at least one pancreatic multipotent or unipotent gene regulator is capable of driving transformation of the cell of a first type into the pancreatic multipotent or unipotent cell; and placing or maintaining the cell in a pancreatic cell culture medium and maintaining intracellular levels of the at least one pancreatic multipotent or unipotent gene regulator for a sufficient period of time to allow a pancreatic multipotent or unipotent cell to be obtained.

Methods of manufacturing T cells to improve their efficacy, persistence, memory function, and/or antigen stimulated survival are provided. Methods of manufacturing T cells to improve production of Central Memory T (Tcm) cells are provided. Methods may include culturing or treating T cells with one or more histone deacetylase inhibitor (HDACi) and interleukin-21 (IL-21), with one or more kinase inhibitor, such a tyrosine kinase inhibitor, and/or with one or more AKT inhibitor (AKTi).

The present disclosure provides methods for re-stimulating TIL populations that lead to improved phenotype and increased metabolic health of the TILs and provides methods of assaying for TIL populations to determine suitability for more efficacious infusion after re-stimulation.

The present disclosure provides methods for re-stimulating TIL populations that lead to improved phenotype and increased metabolic health of the TILs and provides methods of assaying for TIL populations to determine suitability for more efficacious infusion after re-stimulation.

In some embodiments, compositions and methods relating to isolated artificial antigen presenting cells (aAPCs) are disclosed, including aAPCs comprising a myeloid cell transduced with one or more viral vectors, such as a MOLM-14 or a EM-3 myeloid cell, wherein the myeloid cell endogenously expresses HLA-A/B/C, ICOS-L, and CD58, and wherein the one or more viral vectors comprise a nucleic acid encoding CD86 and a nucleic acid encoding 4-1BBL and/or OX40L and transduce the myeloid cell to express CD86 and 4-1BBL and/or OX40L proteins. In some embodiments, methods of expanding tumor infiltrating lymphocytes (TILs) with aAPCs and methods of treating cancers using TILs after expansion with aAPCs are also disclosed.

The present disclosure relates to methods for expanding populations of hematopoietic stem cells (HSCs) using a genetically engineered human fetal liver niche and compositions of purified ex vivo expanded HSCs. Also provided herein are methods of using such expanded HSC cell populations for clinical applications including allogeneic hematopoietic stem cell transplantation and for drug discovery and modeling human liver development.

Disclosed are compositions and methods for suppressing without killing alloreactive and/or autoreactive lymphocytes. The methods can be used for preventing graft versus host disease (GVHD) in subjects receiving donor cells or treating autoimmunity. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to suppress alloreactive or autoreactive lymphocytes. Also disclosed are regulatory T cells that are engineered to express these CARs. Therefore, also disclosed are methods of suppressing alloreactive or autoreactive lymphocytes in a subject in need thereof that involves adoptive transfer of the disclosed regulatory T cells engineered to express the disclosed CARs.