Disclosed herein are methods and platforms for increasing utility and efficacy of a cellular vaccine. Specifically, disclosed are steps that optimize ex vivo B cell expansion and boost host in vivo immunity. Also disclosed is a platform for enhancing effectiveness of antigen presentation and antigen-specific immune responses. Also disclosed is a method for enhancing effectiveness of APCs in a subject. Also disclosed are vaccines and kits based on the platform.

The present invention relates to therapeutic uses of ex vivo generated Foxp3+ regulatory T cells. The inventors showed the presence of Foxp3+ expressing T cells in tumor infiltrating lymphocytes (TILs) isolated from luminal-B breast cancer. The inventors performed an ex vivo generation and expansion of specific CD3+ TCRy8+ expressing Foxp3: CD3+ TCRy8+ T cells maintain their Foxp3 level and their suppressive activity, after a further 21-day-culture. They also showed that tumor Ag-specific CD3+ TCR Va24+ T cells maintain their ability to perform suppressive function in pro-inflammatory conditions. In particular, the present invention relates to immunotherapeutic uses of at least one of ex vivo generated Foxp3+regulatory T cells population selected among a MHCII restricted CD4+Foxp3+regulatory T cells population, a y8 Foxp3+regulatory T cells population and an invariant Foxp3+regulatory T cells population.

The application relates to biological components, methods, systems, and kits for modulating immune responses. The disclosed biological components include genetically modified cells comprising an inserted exogenous sequence in a major histocompatibility complex (MHC)-associated gene. The inserted exogenous sequence encodes a peptide and the genetically modified cells express a fusion protein comprising the peptide and at least a portion of the polypeptide encoded by the MHC-associated gene to form a modified MHC complex. The genetically modified cells may present the peptide as an antigen associated with the MHC complex and may be utilized in methods for modulating T cell activity, inducing an immune response, and inducing a tolerogenic response. As such, the disclosed biological components, methods, systems, and kits may be utilized in order to treat and/or prevent a disease or disorder in a subject in need thereof and to screen and validate clinically relevant antigens.

Methods are provided for generating DLL4-expressing immune cells. The invention also includes cellular compositions of dendritic and T cells produced by these methods. The immune cells of the invention can be used widely as components in many diagnostic and therapeutic systems, including improved vaccines to reduce the risk of graft versus host disease.

Disclosed herein are hypoimmunogenic T cells having reduced expression of RhD antigen for administering to a patient. In some embodiments, the cells are propagated from a primary T cell or a progeny thereof or are derived from an induced pluripotent stem cell (iPSC). In some embodiments, the cells exogenously express CD47 proteins and exhibit reduced expression of MHC class I proteins, MHC class II proteins, or both. In some embodiments, the cells exogenously express one or more chimeric antigen receptors.

The present invention provides antigen-binding proteins that specifically bind to an HLA-displayed human papillomavirus (HPV) peptide, and therapeutic and diagnostic methods of using those binding proteins.

In certain aspects, provided herein are compositions and methods for treating cancer. The methods of the present disclosure comprise administering to a subject in need thereof a NK cell expressing a CAR in combination with an antigen-binding molecule that binds to a tumor antigen, wherein the CAR-NK cell targets tumor cells through binding to the antigen-binding molecule.

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.

Disclosed herein are engineered cells and/or hypoimmunogenic cells including engineered cells and/or hypoimmunogenic stem cells, engineered cells and/or hypoimmunogenic cells differentiated therefrom, and engineered cells and/or hypoimmunogenic CAR-T cells (primary or differentiated from engineered and/or hypoimmunogenic stem cells) and related methods of their use and generation comprising reduced expression of one or more Y chromosome genes and reduced expression of MHC I and/or MHC II human leukocyte antigen molecules and overexpression of CD47. Provided herein are cells further exhibiting reduced expression of T-cell receptors.

The present disclosure provides a dendric cell tumor vaccine comprising a chimeric antigen receptor for activating the dendritic cell and a tumor antigen. The present disclosure also provides compositions and methods of making the dendritic cell tumor vaccine, and the methods of using the dendritic cell tumor vaccine to treat cancer.