Compositions and methods are disclosed herein for producing one or more immunoglobulins in an isolated cytotoxic B lymphocyte cell line. An isolated cell line includes an isolated B lymphocyte cell line capable of expressing at least one exogenously incorporated membrane immunoglobulin capable of binding to a first antigen and at least one endogenous secreted immunoglobulin capable of binding to a second antigen, and further capable of expressing at least one exogenously incorporated recombinant B cell receptor that signals for expression of cytotoxic effector molecules.

The disclosure provides for compositions and methods comprising cell-derived vesicles induced from cells that have been genetically engineered or infected to express specific antigen(s), and uses thereof, including as a cell-free, cell-like vaccine.

The present invention relates to methods for targeted insertion of at least one nucleic acid sequence/s of interest into a target genomic locus of a mammalian cell. More specifically, the methods of the invention are based on using nucleic acid cassettes comprising the nucleic acid sequence/s of interest and at least one recognition signal sequence (RSS), for insertion of the nucleic acid sequence of interest into the target genomic locus that is mediated by RAG-catalyzed recombination. The invention further provides cassettes, vectors and vehicles and cells comprising said cassettes, compositions and uses thereof in immunotherapy.

This invention provides novel carbonic anhydrase (CAIX) nucleic acid and peptide sequences, as well as related methods and compositions, including anti-cancer immunogenic agent(s) (e.g. vaccines and chimeric molecules) that elicit an immune response specifically directed against cancer cells expressing a CAIX antigenic marker. The novel CAIX variant and related compositions are useful in a wide variety of treatment modalities including, but not limited to protein vaccination, DNA vaccination, and adoptive immunotherapy.

Described herein are compositions of matter and methods for treating cancer. The compositions comprise altered human telomerase polypeptides containing T cell epitopes that have been altered to increase immunogenicity. The methods comprise administration of the polypeptides or nucleic acids, such as DNA or RNA encoding the polypeptides, to individuals afflicted with, or at risk of, developing cancer.

Methods for improving engraftment of donor cells in a subject thereof are provided. Such methods can comprise providing donor cells that have been modified to express a first isoform of a target protein (e.g., interleukin-2 receptor subunit gamma (IL2RG)) that is functionally indistinguishable but immunologically distinguishable from a second isoform of the target protein, administering the donor cells to the subject, and then selectively inhibiting host cells in the subject based on their expression of the second isoform of the target protein, thereby improving engraftment of donor cells in the subject. Also provided are combinations for administration to a subject in need thereof, wherein the combination comprises (1) a population of donor cells modified to express a first isoform of a target protein (e.g., IL2RG) and (2) an antagonist (e.g., anti-IL2RG antigen-binding protein) that specifically binds to a second isoform of the target protein but does not specifically bind to the first isoform of the target protein.

Embodiments of the disclosure include methods and compositions related to targeting of antigen-expressing cells with particular engineered antigen receptors expressed by immune cells. In specific embodiments, immune cells specifically engineered to express particular antigen receptor constructs are cultured in the presence of kinase inhibitors and exhibit reduced fratricidal activity compared to immune cells cultured in the absence of kinase inhibitors. In some embodiments, the genetically engineered immune cells having reduced fratricidal activity are used to treat diseases in subjects, and the fratricidal activity of the genetically engineered immune cells is restored in vivo after substantial elimination of the diseased cells, resulting in elimination of the genetically engineered immune cells.

The present disclosure relates to chimeric engulfment receptor molecules, host cells modified to include the phagocytic engulfment molecules, and methods of making and using such receptor molecules and modified cells.

The present invention provides methods compositions and methods of preparing autologous B-cells that secrete a monoclonal of interest useful in immunotherapy.

The present invention relates to a phenotypically distinct CD1d.sup.highCD5.sup.+ B cell subset that regulates T cell mediated inflammatory responses through the secretion of interleukin-10 (IL-10). The invention also relates to the use of these IL-10 producing regulatory B cells in the manipulation of immune and inflammatory responses, and in the treatment of disease. Therapeutic approaches involving adoptive transfer of these regulatory B cells, or expansion of their endogenous levels for controlling autoimmune or inflammatory diseases and conditions are described. Ablation of this subset of regulatory B cells, or inhibition of their IL-10 production can be used to upregulate immunodeficient conditions, and/or to treat tumors/cancer. Diagnostic applications also are encompassed.