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.

Devices, systems, and methods can be used for the automated production of dendritic cells (DC) from dendritic cell progenitors, such as monocytes obtained from peripheral blood, and the automated generation of immunotherapeutic products from those dendritic cells, all within a closed system. The invention makes it possible to obtain sufficient quantities of a subject's own DC for use in preparing and characterizing vaccines, for activating and characterizing the activation state of the subject's immune response, and to aid in preventing and/or treating cancer or infectious disease.

Provided is a method of treating a cancer in an individual using activated T cells or PBMCs induced by antigen presenting cells (such as dendritic cells) loaded with a plurality of tumor antigen peptides. The method may further comprise administration of the antigen presenting cells loaded with the plurality of tumor antigen peptides to the individual. The methods may be used singly or in combination with an immune checkpoint inhibitor. Also provided are precision therapy methods customized for the individual using neoantigen peptides or based on the mutation load in the tumor of the individual, methods of preparing the activated T cells, methods of monitoring the treatment, methods of cloning tumor-specific T cell receptors, an isolated population of cells comprising the activated T cells, and compositions and kits useful for cancer immunotherapy.

In vitro biomimetic models of the neonatal immune system are provided along with methods of using the models in pre-clinical assessment of infant immune cell-mediated and humoral responses to immunogenic stimulation, such as vaccination. The models include one comprising cord blood-derived T follicular helper cells and B cells, and one comprising cord blood-derived dendritic cells and CD4+ T cells. The models can be used, for example, to assess candidate vaccines via analysis of cellular responses to antigen and vaccine exposure.

The present disclosure provides ex vivo methods which employ modified cells of leukemic origin to enhance the efficacy of adoptive cell therapy.

Cell-based compositions and methods for targeting and treating human diseases, including cancers and infectious diseases, are provided, wherein exogenous intracellular sarcosine is used for improved delivery of the composition.

The invention relates to pharmaceutical compositions that contain COVID-19 peptide specific cytotoxic T cells, and to methods for treating or preventing COVID-19 infection.

This disclosure relates to the combination of soluble β-glucan and immune suppression-relieving agents that affect the tumor microenvironment. Soluble β-glucan promotes an immunostimulatory environment, which allows enhanced effectiveness of anti-angiogenics, checkpoint inhibitors including non-tumor targeting antibodies.

Provided is a method of treating a cancer in an individual using activated T cells or PBMCs induced by antigen presenting cells (such as dendritic cells) loaded with a plurality of tumor antigen peptides. The method may further comprise administration of the antigen presenting cells loaded with the plurality of tumor antigen peptides to the individual. The methods may be used singly or in combination with an immune checkpoint inhibitor. Also provided are precision therapy methods customized for the individual using neoantigen peptides or based on the mutation load in the tumor of the individual, methods of preparing the activated T cells, methods of monitoring the treatment, methods of cloning tumor-specific T cell receptors, an isolated population of cells comprising the activated T cells, and compositions and kits useful for cancer immunotherapy.

The present invention relates to methods of obtaining a mixed population of human XCR1+ and plasmacytoid dendritic cells from hematopoietic stem cells. Human DC subsets are rare in blood and other tissues, difficult and expensive to isolate, and fragile. Hence, to advance on deciphering their functions and their molecular regulation, there is a strong need for relevant in vitro models. The inventors developed a new protocol allowing simultaneous generation of the various human DC subsets in vitro from hematopoietic progenitors. In particular, the present invention relates to a method of obtaining a mixed population of human XCR1.sup.+ and plasmacytoid dendritic cells said method comprising the steps of i) culturing a population of hematopoietic stem cells (HSC) or committed hematopoietic precursor cells in the presence of a Notch ligand, and thereafter, ii) isolating human XCR1.sup.+ and plasmacytoid dendritic cells from the culture.