Provided herein are methods and systems for bio-printing of three-dimensional organs and organoids. Also provided herein are bio-printed three-dimensional organs and organoids for use in the generation and/or the assessment of immunological products and/or immune responses. Also provided herein are methods and system for bio-printing three-dimensional matrices.

This present disclosure relates to systems, methods, and compositions useful for profiling T cell receptor (TCR) and B cell receptor (BCR) repertoire using next-generation sequencing (NGS) methods. The present disclosure also relates to systems and methods for diagnosing, treating, or predicting infection, disease, medical conditions, therapeutic outcome, or therapeutic efficacy based on the TCR/BCR profile data from a subject in need thereof.

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.

Sebaceous gland-like organoids comprising a Blimp1 positive cell are provided. Methods of producing the organoids and using the organoids to test a skin drug are also provided; as are methods of treating acne.

The invention relates to a method for the in vitro generation of antigen-specific antibodies or cells producing thereof, said method comprising culturing B cells with an antigen-coated carrier for at least 3 days, wherein said antigen-coated carrier has a size between 0.5 μm and 20 μm, and co-culturing the B cells obtained from step a) with CD4+ T cells for at least 3 days. Thus, high-affinity class-switched immunoglobulins of clinical and diagnostic interest are produced in vitro.

The invention relates to a new method for in vitro expansion of CD4.sup.+CD25.sup.HighCD127.sup.−/LowFoxP3.sup.+ Tregs, wherein the process of Treg expansion takes place permanently or temporarily at a temperature below 37° C., optimally at a temperature of 33° C., the isolated Tregs are expanded in SCGM or X-vivo-20 medium supplemented with human serum or with foetal bovine serum, and magnetic beads coated with anti-CD3 and anti-CD28 antibodies at 1:1 (cell:bead) ratio and interleukin-2 are added to the culture.

The present invention provides an in vitro method for the manufacture of a dendritic cell (DC) cancer vaccine, said method comprising the steps of: (i) providing a plurality of phagocytosable particles, wherein each phagocytosable particle comprises a core and an antigenic construct tightly associated to the core, wherein the antigenic construct comprises at least one epitope peptide having an amino acid sequence corresponding to an amino acid sequence of a part of a protein or peptide known or suspected to be expressed by a cancer cell in a subject; (ii) providing a sample of DCs; and (iii) contacting the sample of DCs with the plurality of phagocytosable particles in vitro and under conditions allowing for the phagocytosis of at least one phagocytosable particle by a DC. The present invention also provides a DC cancer vaccine produced by the method of the invention, and the use a DC cancer vaccine of the invention as a medicament and for the ex vivo expansion of anticancer T-cells.

The present disclosure describes, in part, a Micro-organosphere immune-oncology assay and methods of making and using same. The assay quickly measures the potency of effector immune cells, such as tumor infiltrating lymphocytes, at killing a patient's tumor cells. Understanding the potency of effector immune cells is critical for adoptive T cell therapy.

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.

Provided methods of obtaining a plurality of T cell receptors specifically recognizing a target tumor antigen peptide from an individual that has clinically benefitted from an immunotherapy, such as Multiple Antigen Specific Cell Therapy. Also provided tumor-specific TCRs, engineered immune cells expressing the TCRs and methods of treating a disease using the engineered immune cells.