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.

Provided are age-modified cells and method for making age modified cells by reducing or increasing the level of genomic nucleic acid methylation in the cells. The aging and/or maturation process can be accelerated or reduced and controlled for young, aged, mature and/or immature cells, such as a somatic cell, a stem cell, a stem cell-derived somatic cell, including an induced pluripotent stem cell-derived cell, by reducing or increasing the level of genomic nucleic acid methylation in the cells. Methods described by the present disclosure can produce age-appropriate cells from a somatic cell or a stem cell, such as an old cell, young cell, immature cell, and/or a mature cell. Such age-modified cells constitute model systems for the study of late-onset diseases and/or disorders.

Compositions disclosed herein, and methods of use thereof included those for inhibiting or reducing the incidence of cytokine release syndrome or cytokine storm in a subject undergoing CAR T-cell therapy, methods of treating a cancer or tumor, methods of reducing tumor load, methods of reducing the size or growth rate of a cancer or a tumor, and methods of extending of the survival of a subject suffering from a cancer or tumor, wherein the subjects are administered compositions comprising apoptotic cells or apoptotic cell supernatants. Compositions and methods of use thereof may increase the efficacy of a CAR T-cell cancer therapy. Disclosed herein are also compositions and methods of use thereof for decreasing or inhibiting cytokine production in a subject experiencing cytokine release syndrome or cytokine storm. In certain instances compositions may include additional chemotherapeutic or immunomodulatory agents.

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 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 disclosure relates generally to the manufacture of regulatory T cells (Tregs) for use in immunotherapy. In particular, the present disclosure relates to robust approaches for the expansion of alloantigen-reactive Tregs ex vivo. Alloantigen-reactive Tregs produced in this way are suitable for the induction and/or maintenance of immunologic tolerance in recipients of allogeneic transplants.

The invention features methods of producing compositions enriched in Tregs and methods for treating immunological disorders using these compositions. The invention also features methods for producing compositions enriched in lymphocytes and depleted of Tregs and the use of these compositions in the treatment of proliferative disorders.

Methods are provided for stimulating ovarian follicles in a mammal through activation of the mTor signaling pathway.

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.

A somatic stem cell that is CD10+, CXCR4+, and CD31+ and another somatic stem cell that is CD105+, CD44+, and nestin+. Also disclosed are both a method of preparing these stem cells and a method of using them to treat degenerative diseases, e.g., a muscle-degenerative disease. The invention further includes making and using liver cells derived from the somatic cell that is CD105+, CD44+, and nestin+.