Methods of reducing T cell activation including co-culturing with T cells, term amniotic fluid mesenchymal stem cells (TAF-MSCs) isolated from term human amniotic fluid. Other aspects relate to methods of inhibiting macrophage polarization toward the M1 pro-inflammatory phenotype including co-culturing with macrophages TAF-MSCs isolated from term human amniotic fluid. Other aspects relate to methods of inhibiting cytokine secretion from activated Peripheral Blood Mononuclear Cell (PBMC) including co-culturing with the PBMC tissue-typed TAF-MSCs isolated from human amniotic fluid. Other aspects relate to methods of differentiating TAF-MSC including: obtaining TAF-MSC cells from term amniotic fluid, plating the TAF-MSC cells in limiting dilution to obtain expanded colonies from single cells, and transferring the cells to a differentiation media that contains one or more factor to differentiate the TAF-MSC cells.

The present invention aims to increase cytotoxic activity of an immunocompetent cell to thereby enhance a therapeutic effect against diseases such as cancers, and provides an immunocompetent cell having decreased diacylglycerol kinase activity, which cell expresses a fusion protein including IL-15 and an IL-15 receptor α subunit, and which cell expresses a chimeric antigen receptor.

The invention involves generating a T cell response to subdominant antigens and using the cells to therapeutically change the cellular homeostasis and nature of the immune response. In a preferred embodiment, the cells are generated outside of the patient avoiding the influence of the patient's immunologic milieu. By stimulating and growing the T cells from a patient in a tissue culture to one or more subdominant antigens and the transplanting them into the patient, if enough cells are expanded and transplanted, the transplanted cells overwhelm the endogenous dominant T cells in the response to either break or induce immune tolerance or otherwise modify the immune response to the cells or organism expressing that antigen. When the memory cells are established they are then reflective of this new immunodominance hierarchy so that the desired therapeutic effect is long lasting. In effect, the transplantation exogenously generated T cells reactive to the subdominant antigens is recapitulating priming and rebalancing the patient's immune response to target previously subdominant antigens in the cells or organism to produce a therapeutic benefit.

The invention relates to purified, tissue-specific progenitors, methods of making and using such tissue-specific progenitors.

The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to 11 novel peptide sequences and their variants derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

A method for coordinating the manufacturing of an expanded cell therapy product for a patient may include receiving a cell order request to expand the cell therapy product for the patient; generating a patient-specific identifier or cell order identifier associated with the cell order request; and initiating a process to expand the cell therapy product from at least some of a solid tumor obtained from the patient. If acceptance parameters for the expansion cell therapy product do not meet certain acceptance criteria at a second time point subsequent to a first time point in the expansion process, it is determined whether re-performing the expansion of the cell therapy product using the cell expansion technique is possible from the first time point based on the acceptance parameters at the second time point. If such re-performing the expansion is possible, patient treatment events that use the expanded cell therapy product are rescheduled.

The present invention relates to a topical pharmaceutical preparation for treating an inflammatory skin condition, preferably a condition associated with ischemia, comprising a supernatant of a physiological solution obtainable by cultivating peripheral blood mononuclear cells (PBMCs) or a subset thereof in a physiological solution free of PBMC-proliferating and PBMC-activating substances for at least 1 h.

Universal human induced pluripotent stem cells (universal hiPSCs) and a method of forming the same are provided in the disclosure, including the following steps: providing a first cell group including human stem cells; providing a second cell group including human mononuclear cells; in some embodiments, the second cell group further includes human stem cells, in which the human stem cells of the second cell group are allogenic cells from the first cell group; mixing the first cell group and the second cell group to form cell mixture; maintaining the cell mixture at a temperature below 30° C. for at least one day; reprogramming the human stem cells of the cell mixture to obtain universal hiPSCs. The universal hiPSCs includes human leukocyte antigen-1 (HLA class I) gene and human leukocyte antigen-2 (HLA class II) gene, but no HLA class I and HLA class II expressions.

Disclosed herein are methods for identifying immunomodulatory genes. In some embodiments, the method comprises of screening a candidate gene comprising: a) expressing an exogenous cellular receptor, or a functional portion thereof, in a plurality of immune cells; b) introducing into said plurality of immune cells: i. a guiding polynucleic acid, or a nucleic acid encoding said guiding polynucleic acid, wherein said guiding polynucleic acid targets said candidate gene; and ii. an exogenous nuclease, or a nucleic acid encoding said exogenous nuclease; thereby generating a plurality of engineered immune cells comprising a genomic disruption in said candidate gene; c) contacting said plurality of engineered immune cells with a plurality of cells expressing a cognate antigen of said exogenous cellular receptor or a functional portion thereof, thereby performing an in vitro assay; and d) determining a readout of said in vitro assay.

The present invention refers to a method for inducing pluripotent stem cells starting from somatic cells isolated from healthy and/or diseased individuals. The diseased individual is preferably affected by a genetic disease such as type A hemophilia, and the somatic cells from the diseased individual are genetically corrected for the mutation causing the disease preferably after being reprogrammed by the method of the present invention. A further aspect of the present invention refers to a method for differentiating induced pluripotent stem cells or embryonic stem cell-like into endothelial cells. Moreover, the present invention refers to the use of these cells as a medicament for treating a disease, in particular, a genetic disease such as type A hemophilia.