The present disclosure relates, at least in part, to mycobacterial polynucleotides and polypeptides, to fragments or variants thereof, to cells comprising the mycobacterial polynucleotides and polypeptides, to cells comprising the mycobacterial polynucleotides and polypeptides, that are engineered to expand T-cells ex vivo, and to methods of use thereof.

Methods are disclosed for producing defective ribosomal products (DRiPs) in blebs (DRibbles) by contacting cells with a proteasome inhibitor, and in some examples also an autophagy inducer, thereby producing treated cells. DRibbles can be used to load antigen presenting cells (APCs), thereby allowing the APCs to present the DRiPs and antigenic fragments thereof. Immunogenic compositions that include treated cells, isolated DRibbles, or DRibble-loaded APCs are also disclosed. Methods are also provided for using treated cells, isolated DRibbles, or DRibble-loaded APCs to stimulate an immune response, for example in a subject. For example, DRibbles obtained from a tumor cell can be used to stimulate an immune response against the same type of tumor cells in the subject. In another example, DRibbles obtained from a pathogen-infected cell or cell engineered to express one or more antigens of a pathogen can be used to stimulate an immune response against the pathogen in the subject.

A non-immunogenic selection epitope may be generated by removing certain amino acid sequences of the protein. For example, a gene encoding a truncated human epidermal growth factor receptor polypeptide (EGFRt) that lacks the membrane distal EGF-binding domain and the cytoplasmic signaling tail, but retains an extracellular epitope recognized by an anti-EGFR antibody is provided. Cells may be genetically modified to express EGFRt and then purified without the immunoactivity that would accompany the use of full-length EGFR immunoactivity. Through flow cytometric analysis, EGFRt was successfully utilized as an in vivo tracking marker for genetically modified human T cell engraftment in mice. Furthermore, EGFRt was demonstrated to have cellular depletion potential through cetuximab mediated antibody dependent cellular cytotoxicity (ADCC) pathways. Thus, EGFRt may be used as a non-immunogenic selection tool, tracking marker, a depletion tool or a suicide gene for genetically modified cells having therapeutic potential.

The present invention relates to a polypeptide for delivering an antigen to immune cells and, specifically, to: a novel polypeptide comprising a cell membrane penetrating peptide and a peptide binding to a surface molecule on immune cells; a fusion polypeptide in which an antigen is coupled to the polypeptide; a nucleic acid coding for the polypeptide or the fusion polypeptide; an immune cell sensitized with the fusion polypeptide or the nucleic acid coding therefor; and an immunotherapeutic agent, antitumor or anticancer vaccine, and a composition for treating a tumor or cancer, each comprising the immune cell.

Provided is a dendritic cell therapeutic agent, and more particularly, a composition which include dendritic cells activated by peptides including a telomerase-derived peptide, the composition administered to treat an individual having disease and disorder symptoms which require target-specific treatments. Also, provided is a therapeutic method effective on diseases requiring target-specific immunotherapy. In the method, co-administration of the dendritic cell therapeutic agent and an immunotherapeutic agent including the telomerase-derived peptide results in decreased factors causing one of the disease and disorder symptoms requiring the target-specific treatment, such as cancer, in a tumor disease treatment.

Provided herein are antibodies and chimeric priming receptors that bind PSMA and antibodies and chimeric antigen receptors that bind CA9. Also provided are systems of chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9, cells expressing such systems, and methods of use thereof.

A non-immunogenic selection epitope may be generated by removing certain amino acid sequences of the protein. For example, a gene encoding a truncated human epidermal growth factor receptor polypeptide (EGFRt) that lacks the membrane distal EGF-binding domain and the cytoplasmic signaling tail, but retains an extracellular epitope recognized by an anti-EGFR antibody is provided. Cells may be genetically modified to express EGFRt and then purified without the immunoactivity that would accompany the use of full-length EGFR immunoactivity. Through flow cytometric analysis, EGFRt was successfully utilized as an in vivo tracking marker for genetically modified human T cell engraftment in mice. Furthermore, EGFRt was demonstrated to have cellular depletion potential through cetuximab mediated antibody dependent cellular cytotoxicity (ADCC) pathways. Thus, EGFRt may be used as a non-immunogenic selection tool, tracking marker, a depletion tool or a suicide gene for genetically modified cells having therapeutic potential.

The present invention relates to a pharmaceutical combination of compositions for use in the treatment or prevention of a disease having cells bearing a target antigen as a vaccine and to a method for vaccination of a mammal, especially of a human for raising a cellular immune response directed against cells of the mammalian recipient, especially human recipient, which cells express a target antigen. The target antigen can e.g. be an autoantigen like a malignant antigen, i.e. a tumour-specific antigen. The pharmaceutical combination of compositions comprises a first composition and a second composition, wherein the second composition is for administration to recipient subsequent to the administration of the first composition, e.g. 2 to 10 days after the first composition. The pharmaceutical combination of compositions has the advantage of raising an effective antigen-specific T-cell response against cells bearing a target antigen that can be a malignant autoantigen, e.g. for raising an antigen-specific T-cell response against cells bearing a tumour-antigen. A further advantage is that the pharmaceutical combination of compositions can raise an antigen-specific T-cell response within a comparatively short time.

The application of induced pluripotent stem cells (iPSCs) to generate adoptive cell therapy products and usage of iPSCs for screening potential toxicity of immune receptors are described herein. In some aspects, iPSCs and cells differentiated therefrom are provide which do not express a HLA gene (e.g., HLA-A).

A composition includes genetically modified leukocytes, the modification including a deleted or silenced prostacyclin receptor PTGIR that confers resistance to the immunosuppressive effects of prostanoids.