A seed cell medium of a tumor-infiltrating lymphocyte and an application thereof. The medium contains a cell culture component, a cell factor, and an immune checkpoint antibody or an antigen-binding fragment thereof. The cell factor includes IL-2; an immune checkpoint includes PD-1, LAG-3, TIGIT, and/or CTLA-4; and the cell culture component is a serum medium or a serum-free medium. The seed cell medium accelerates a culture of a seed cell of the tumor-infiltrating lymphocyte and shortens the amplification time required by the tumor-infiltrating lymphocyte.

This disclosure relates to methods of preserving mesenchymal stromal/stem cells (MSCs) for use in clinical applications. In certain embodiments, this disclosure relates to methods of preserving MSCs comprising mixing MSCs with interferon-gamma prior to cryopreserving, freezing, or cooling the MSCs to a temperature below zero degrees Celsius.

The present invention is targeted towards reinvigorating exhausted Tumor Infiltrating Lymphocytes (TILs) in vitro by co-culturing excised TIL containing tumor fragments with checkpoint inhibitors, stimulating the TILs with other interleukins known to revert T cell exhaustion), and/or inhibiting the effect of regulatory T cells secreted factors (such as IL-10) thereby creating a favorable tumor microenvironment (TME) where exhausted T-cells can expand faster and to higher numbers than currently established TIL expansion protocols.

As disclosed herein, SIRPα is integral to immuno-evasion by many different cancer types as well as cancer resistance to therapies, and reducing SIRPα levels on can bolster antigen acquisition, processing, and presentation, decrease TME immunosuppression and thereby promote tumor-specific T cell activation to eliminate tumors and generate an adaptive immune response consisting of memory T cells, circulating antibodies, and plasma cells, all of which may be specific for neo-antigens in the original cancer. Therefore, disclosed are activated SIRPα.sup.low macrophages that are useful for treating cancers.

Embodiments of the disclosure encompass systems, methods, and compositions for producing exosomes from primed mesenchymal stem cells that are expanded in the presence of IFNγ, TNFα, IL-1β, and IL-17. The systems, methods, and compositions ay occur in an automated cell expansion system that allows for controllable parameters and from which cells and exosomes may be harvested at one or more times as part of a particular regimen. In specific embodiments, the exosomes may be provided to an individual in need thereof, including in some cases when the exosomes comprise one or more therapeutic agents.

Disclosed herein is a kit to produce a personalized vaccine based on autologous dendritic cells. The kit contains all the materials, reagents and information necessary to produce a dose of live dendritic cell vaccine against a pathogen organism, part of a pathogen organism, a toxin, a venom, a structure obtained by recombinant method or chemical synthesis.

Provided is an excellent method for producing an IL-4 non-secreting and IFN-γ secreting (Th1-type) or IFN-γ non-secreting and IL-4 secreting (Th2-type) CD4 single-positive T cell (CD4SP T cell). The method for producing the Th1-type or Th2-type CD4SP T cell of the present invention comprises a step of inducing a CD4 single-positive T cell from a hematopoietic stem cell (HSC) and/or a hematopoietic progenitor cell (HPC) substantially defective in a factor involved in IL-4 secretion or a factor involved in IFN-γ secretion.

Provided herein are methods for obtaining populations of reprogrammed MO-homeostatic tolerogenic microglial cells. The methods include providing an initial population of monocytes, e.g., peripheral blood monocytes (PBMC), from a subject, and reprogramming the cells by maintaining the PBMC in culture ex vivo in the presence of a sufficient amount of transforming growth factor-beta (TGFβ) and interferon-gamma (IFNγ) for a time and under conditions sufficient for the cells to become M0-homeostatic tolerogenic microglia. Also provided are methods of use of these cells, e.g., for the treatment of neurodegenerative diseases associated with inflammation, e.g., Alzheimer's Disease (AD); Multiple Sclerosis (MS), e.g., progressive MS; and Amyotrophic Lateral Sclerosis

Provided are a composition and method for inducing direct conversion from a somatic cell into a myeloid cell and use thereof, in which differentiation from a somatic cell into a myeloid cell can be efficiently induced through the expression of a single direct conversion inducer without undergoing the pluripotency stage of induced pluripotent stem cells, and thus, the composition can be widely used as an effective preventive and therapeutic agent for immune diseases.

In certain example embodiments, the invention provides a method of generating an ex vivo cell-based system comprising dissociating an original tissue sample obtained from a subject into a single cell population; determining an in vivo phenotype of the tissue sample by conducting single-cell RNA analysis on a first portion of the single cells; establishing an ex vivo cell-based system from a second portion of the single cells; and culturing the ex vivo cell-based system in a medium or conditions selected to maintain the in vivo phenotype. In some embodiments, the original tissue sample is a tumor tissue sample, such as a pancreatic ductal adenocarcinoma (PDAC) tumor sample.