The invention relates to a three-dimensional in vitro alveolar lung model comprising essentially the four cells types as follows: alveolar type II epithelial cells able to secrete (lung laying) surfactant, endothelial cells which forms the inner lining of capillaries providing a permeable barrier, dendritic-like cells, such as non-differentiated THP-1, linking innate and adaptive immunity and macrophage-like cells, able to participate to defense mechanisms by ingesting foreign materials by phagocytosis. The invention also relates to a process for preparing said model, and its use for assessing the irritation potential or toxicity of inhalable products such as particles or molecules on the alveolar barrier of lungs, and also for determining and/or predicting the sensitizing effects of inhalable products such as particles or molecules on the alveolar barrier of lungs.

The present invention relates to methods for expanding TILs from tumor tissue using a long first expansion process and a shorter second expansion process. A method for expanding TIL includes obtaining a first population of TILs from a tumor resected from a subject, performing a first expansion for a period of about 21 day to about 35 days by culturing the first population of TILs in a cell culture medium comprising 4-1BB agonist, IL-2, and OKT-3 to produce a second population of TILs, and performing a second expansion for a period of about 7 days to about 10 days by supplementing the cell culture medium of the second population of TILs with antigen presenting cells (APCs) and additional 4-1BB agonist, IL-2, and OKT-3, and culturing to produce a third population of TILs, wherein the third population of TILs is a therapeutic population of TILs.

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.

The invention relates to a method of producing an iPSC-derived Kupffer Cell (IKC). The method may comprise providing a macrophage precursor (preMcp) derived from an induced pluripotent stem cell (iPSC). The macrophage precursor (preM-cp) may be cultured in the presence of a hepatic cue, such as a combination of primary human hepatocyte conditioned media and Advanced DMEM, thereby obtaining the iPSC-derived Kupffer Cell. The iPSC-derived Kupffer Cell may display a biological property of a primary Kupffer cell, such as a primary adult human KC (pKC). The biological activity comprises expression of a macrophage marker such as CD11, CD14, CD68, CD163, CD32, CLEC-4F, ID1 and ID3.

Cell culture systems and methods provide improved immunotherapeutic product manufacturing with greater scalability, flexibility, and automation. Cell culture systems are configured with interchangeable cartridges, allowing versatility and scalability. Systems are configured to have multiple connected cell culture chambers, which allows parallel processing of different types of cells. Gas-impermeable cell culture chambers and methods for generating cells in closed systems prevent contamination and user error. Methods for recycling cell culture medium provide additional efficiencies.

The disclosure provides methods and compositions for affecting the development of antigen presenting cell (APC, e.g., a macrophage or dendritic cell). The methods include maturing an APC, promoting anti-inflammatory phenotype, promoting development of a T regulatory cell (Treg) from a naive T cell. The methods generally include exposing an APC to a tryptophan derived microbiota metabolite (TDMM), such as an anti-inflammatory or pro-mucosal TDMM, and permitting the APC to mature. In some embodiments, the conditioned APC is exposed to a naive T cell to further promote development of a T regulatory cell (Treg). In some embodiments, the TDMM is selected from the group consisting of indole, indole-3-acetate, 5-hydroxyindole, and indole-3-pyruvate.

Compositions disclosed herein, and methods of use thereof included those for treating or preventing SARS-CoV-2 vims infection in a subject in need, including methods of extending of the survival of a subject suffering from COVID-19, and reduction of organ dysfunction or failure due to COVID-19 or associated symptoms. Methods of treating or preventing COVID-19 in a subject in need includes administering compositions comprising early apoptotic cells or early apoptotic cell supernatants. Compositions and methods of use thereof may reduce the negative proinflammatory effect accompanying COVID-19 and symptoms thereof. Further, anti-inflammatory cytokine release may be increased. In certain instances, compositions may include additional agents.

The invention is directed to an isolated population of mammal cells comprising about 75% or higher B-1a regula e PBS-treated tory cells expressing the cell surface inhibitory receptors lympho-cyte-activation gene 3 (LAG-3), programmed cell death protein 1 (PD-1), and C-X-C chemokine receptor type 4 (CXCR4), and secreting interleukin-27 (IL-27). The invention is also directed to methods of preparing and using the cell population to suppress the immune system and/or to treat or prevent diseases.

The present invention includes a functionalized nerve guidance conduit (NGC), methods of making neurotrophic factor-expressing neural crest stem-like cells (NCSC) and/or Schwann cell precursor-like (SCP) cells, methods of making the functionalized nerve guidance conduit, and methods of treating nerve injury using the functionalized nerve guidance conduit.

The invention relates to a new process for manufacturing in vitro antigen-specific T lymphocytes (CellTrAg), marked with intracellular dye and expanded in the presence of monocytes loaded with the antigen and subsequently sorted based on the low intensity of intracellular dye where the low intensity of fluorescence is a marker of antigen-specificity in that a loss of fluorescence correlated with the intensity of proliferation. The antigen specificity is assessed in functional tests in which antigen-specific lymphocytes sorted on the basis of low fluorescence are more active than non-specific lymphocytes with high fluorescence during sort; activity is defined in the case of regulatory T lymphocytes as inhibition of effector lymphocyte function and in the case of T effector lymphocytes as enhancing the characteristics of these cells such as proliferation, production of cytokines and cytotoxic factors.