The present disclosure relates to methods for profiling subject specific and personalized T cell receptor (TCR) repertoires using a single-cell sequencing method. More particularly, disclosed are methods for determining binding of T cell receptors to subject specific neoantigens. In addition, the techniques herein may identify the antigenic targets of T cell receptors in the context of tumor neoantigens. Moreover, the present disclosure enables the discovery of T cell targets in numerous diseases, with implications for understanding the basic mechanisms of the mammalian immune response and for developing antigen-specific diagnostic markers and therapies. Finally, cloned TCRs can be used to formulate personalized immunotherapies for those inflicted with a disease, such as cancer.

Provided herein are engineered red blood cells expressing rare blood antigen group profiles, and methods of making use the same, are described. Also provided are recombinant reagent red blood cells that express or lack the expression of at least one protein (e.g., a blood group antigen) on its surface and uses thereof.

The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.

Natural killer cells are differentiated to an intraepithelial innate lymphoid cells (ielLC1)-like cell, with an increase in cytotoxic activity. Specifically, the disclosure provides a method for differentiating mammalian natural killer cells to adapt an ielLC1-like phenotype, the method comprising: differentiating peripheral natural killer (NK) cells in the presence of IL-15 and epithelial cells or plate coatings that mimic features of epithelial cells, to generate CD49a+ CD103+ cells having features and phenotype of ielLC1s, with enhanced cytotoxic activity and expression of Th1 type cytokines.

The present disclosure provides compositions and methods for the generation of an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. Generally, the composition and methods of the disclosure comprise three steps: a “design process” comprising one or more in silico bioinformatics steps to select and generate a library of potential antigens for use in the immunogenic composition; a “formulation process”, comprising in vitro testing of potential antigens, using various biochemical assays, and further combining two or more antigens to generate one or more immunogenic compositions; and an “administering” step, whereby the immunogenic composition is administered to a host animal, immune cell, subject or patient. Further steps may also be included, such as the isolation and production of antibodies raised by host immune response to the immunogenic composition.

The present invention relates to a targeting module comprising a chemically synthesized peptide binding moiety specific for a human cell surface protein or protein complex, a kit comprising the targeting module and a vector or a cell comprising a nucleic acid encoding a universal chimeric antigen receptor and the use for the treatment of cancer, infections and autoimmune disorders.

Provided are methods of making and delivering vaccine compositions using an enucleated cell-based platform. Methods of clearing pathogenic infections in a subject using the enucleated cell-based platform is also provided. Such enucleated cell-based platform reduces the vaccine development timeline as compared with conventional biological vaccines, and improves vaccine efficacy.

The present invention relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.

Provided herein are cytoplasts, compositions comprising cytoplasts, methods of using cytoplasts, and methods of treating a subject, such as providing benefits to a healthy or unhealthy subject, or treating or diagnosing a disease or condition in a subject. In some embodiments, methods of treating a subject include: administering to the subject a therapeutically effective amount of a composition comprising a cytoplast. Also, provided herein are compositions (e.g., pharmaceutical compositions) that include a cytoplast. Also, provided herein are kits comprising instructions for using the compositions or methods.

Combination therapeutics for the treatment of cancer include the use of immune effector cells, IL-15 based superagonists and one or more immunotherapeutic agents such as Bacillus Calmette-Guerin (BCG).