Modified natural killer 92 (NK-92) cells and their use in cancer therapy, in particular for the prevention or treatment of solid tumours such as sarcomas, carcinomas, melanoma and lymphoma, and non-solid tumours such as leukaemia and related disorders. Embodiments of the invention further relate to the use of the modified NK-92 cells for in vitro diagnosis, diagnostics and/or screening, methods for the preparation of a modified NK-92 that is specific for a target antigen of a target cell in a subject, and to an expression vector, comprising the nucleic acid sequences of an antigen-specific functional T cell receptor (TCR), CD3, CD4 and/or CD8.

Provided herein are, inter alia, CD6 targeting CAR-T cell compositions and methods useful for treating autoimmune diseases (e.g., Type I diabetes).

A trifunctional molecule comprising a target-specific ligand, a ligand that binds a protein associated with the TCR complex and a T cell receptor signaling domain polypeptide is provided. The ligand that binds a protein associated with a TCR complex is UCHT1 with a Y177 mutation. Engineering T cells with this novel receptor engenders antigen specific activation of numerous T cell functions, including cytokine production, degranulation and cytolysis.

The present invention relates, in part, to chimeric proteins which include the extracellular domain of V-set and immunoglobulin domain-containing protein 8 (VSIG8) and their use in the treatment of diseases, such as immunotherapies for cancer and/or inflammatory diseases.

Chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain that includes chlorotoxin or a related toxin, or a variant of chlorotoxin or a related toxin, that binds to human glioma or other human tumor cells, a transmembrane region, a costimulatory domain and an intracellular signaling domain are described.

Disclosed are a fusion peptide of CD4 helper T cell epitopes, a nucleic acid encoding the same and an immunogenic composition comprising the same. The epitope fusion peptide comprises a cytomegalovirus epitope and an influenza virus epitope. The epitope fusion peptide can substantially improve the level of cellular immune response to a target immunogen, particularly a weak immunogen, and is an effective means for overcoming the immune tolerance of immune system to an antigen, particularly to a tumor antigen or an infection-related antigen, and is suitable for efficiently enhancing the efficacy of vaccine.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

The disclosure provides, in various embodiments, polynucleotides and vectors comprising sequences encoding a mono-specific or a bi-specific CAR that is capable of binding to a first TAA, or a T-cell engager that is capable of binding to CD3 and a second TAA, or a combination thereof. The disclosure also provides, in various embodiments, T lymphocytes comprising one or more of the polynucleotides or vectors; compositions (e.g., pharmaceutical compositions) and kits comprising one or more of the T lymphocytes; methods of treating a cancer in mammalian subject (e.g., a human), and methods of inducing T cell-mediated cytolysis of cancer cells (e.g., solid tumor cells).

A trifunctional molecule comprising a target-specific ligand, a ligand that binds a protein associated with the TCR complex and a T cell receptor signaling domain polypeptide is provided. The ligand that binds a protein associated with a TCR complex is UCHT1 with a Y182T mutation. Engineering T cells with this novel receptor engenders antigen specific activation of numerous T cell functions, including cytokine production, degranulation and cytolysis.

Disclosed are plasmid and methods for genetically engineering NK cells using Adeno-associated viral (AAV) delivery of a CRISPR/CAS9 system. In some aspects, disclosed herein are method of using such engineering NK cells for treating cancers.