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 provides methods of preparing tumor infiltrating cells engineered to express a pro-inflammatory polypeptide. The pro-inflammatory polypeptide is expressed from the tumor infiltrating cell to counter a generally immunosuppressive state in and around tumors resulting from an imbalance between the number and activation state of immune effector cells versus those of suppressor cells. Delivering the proinflammatory polypeptide via expression from the TICs, as distinct from systemic administration, reduces side effects from increased inflammation at sides remote from a tumor to be treated.

The present invention relates to a substance of formula (I), whereby R.sub.1 is an alkyl or alkenyl group having 6 to 20 carbon atoms; R.sub.2 is H or missing, whereby O is bound via a double bond, R.sub.3 is H or an acyl group -C(O)R.sub.5, whereby R.sub.5 is an alkyl or alkylene group having 1 to 10 carbon atoms, and R.sub.4 is H or a phosphate group for use as a medicament and for use in a method of preventing or treating a subject suffering from an autoimmune disease. The present invention further relates to a method for generating regulatory T cells (Treg cells) in vitro comprising the steps of providing precursor CD4.sup.+T cells, cultivating the precursor CD4.sup.+T cells provided in step 1) in the presence of the substance as defined herein, and, optionally, isolating the generated regulatory T cells (Treg cells).

Methods for production of platelets from pluripotent stem cells, such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are provided. These methods may be performed without forming embryoid bodies or clusters of pluripotent stem cells, and may be performed without the use of stromal inducer cells. Additionally, the yield and/or purity can be greater than has been reported for prior methods of producing platelets from pluripotent stem cells. Also provided are compositions and pharmaceutical preparations comprising platelets, preferably produced from pluripotent stem cells.

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 invention teaches the unexpected finding that treatment of mesenchymal stem cells with inhibitors of mammalian target of rapamycin (mTOR) lead to enhancement of regenerative and/or anti-inflammatory activity of said stem cells. In one embodiment, rapamycin treatment of mesenchymal stem cells (MSC) is associated with enhanced basal and stimulated production of therapeutic factors. In one embodiment other regenerative activities are enhanced by treatment with inhibitors of mTOR such as angiogenesis, neurogenesis, protection from apoptosis, and immune modulation.

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.

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 disclosure provides chimeric antigen receptor (CAR)-T-Rapa cells and methods of making and using them. Specifically, methods of producing T-Rapa cells that can express chimeric antigen receptors is provided.