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.

The present disclosure provides methods for generating MAGE-B2 specific T cells and compositions comprising engineered MAGE-B2-specific T cell receptors. Further provided are methods of treating cancer comprising administering the MAGE-B2-specific T cells.

Provided herein are methods for the production of tissue resident memory-like T cells by the combination of hypoxia and TGFβ. Further provided herein are methods of using the tissue resident memory T cells as adoptive cell therapy.

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 application provides methods of preparing tumor antigen-specific T cells comprising enriching activated T cells from a first co-culture comprising a first population of antigen-loaded dendritic cells loaded and a population of T cells, and co-culturing the enriched activated T cells with a second population of antigen-loaded dendritic cells. Also provided are methods of treating cancer in an individual using the tumor antigen-specific T cells, pharmaceutical compositions and kits for cell-based cancer immunotherapy.

The present disclosure provides methods for re-stimulating TIL populations that lead to improved phenotype and increased metabolic health of the TILs and provides methods of assaying for TIL populations to determine suitability for more efficacious infusion after re-stimulation.

The present invention provides: a novel method for the production of truly fully human monoclonal antibodies against specific antigens of our choice using isolated human blood cells. These antigens may include but are not limited to peptide sequences found in c-met and TMX2 proteins; an antibody specific for c-met protein produced with said method; an antibody specific for TMX2 protein produced with said method; and a new means and method for the diagnosis, prevention and/or cancer treatment by means of the aforementioned antibodies.

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.

A method of generating an isolated population of non graft versus host disease (GvHD) inducing cells comprising a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance inducing cells and/or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) providing a population of at least 70% memory T cells; (b) contacting the population of memory T cells with an antigen or antigens so as to allow enrichment of antigen reactive cells; and (c) culturing the cells resulting from step (b) in the presence of cytokines so as to allow proliferation of cells comprising the Tcm phenotype. Cells generated by the method, pharmaceutical compositions and methods of treatment are also disclosed.

Provided are methods for isolating T-cells with T cell receptors (TCRs) optimized for reactivity to specific peptides and decreased cross-reactivity to non-target peptides. Advantageously, TCRs of the invention can be optimized to target cancer antigens and peptides while having reducing reactivity to healthy cells. Methods of the invention utilize a novel combination of culturing conditions that increase T-cell activation and allow for validation of TCR activity. Culturing conditions of the invention further reduce culturing times generally needed to achieve expanded reactive T-cells. Because of the robust nature of the activation and validation conditions of the present invention, variants of identified TCRs can also be optimized and validated for their response to peptides, including cancer peptides.