The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

Provided herein are methods for expanding populations of regulatory B cells comprising engineering a population of B cells to express CD40 ligand. Also provided herein are methods of treating immune disorders with the regulatory B cells.

The present invention relates to novel immunoregulatory macrophage cells which are useful in the treatment of different immunological and non-immunological diseases and conditions. The cells are characterized by a specific marker and activity pattern which distinguishes them from other cells. The invention also provides a process for preparing the immunoregulatory macrophage cells from blood monocytes. In a still further aspect, the invention relates to a pharmaceutical composition comprising the immunoregulatory macrophage cells of the invention or a sub-cellular fraction thereof. A process for preparing a sub-cellular fraction of an immunoregulatory macrophage cell of the invention is also provided.

The present disclosure provides, inter alia, compositions, cell populations and pharmaceutical compositions and methods useful for the treatment of inflammatory diseases or disorders. In some embodiments, the compositions, cell populations and pharmaceutical compositions and methods comprise a population of CD44.sup.+ cells modified ex vivo via treatment with a CD44 ligand for a period of time sufficient to prime the cells to produce elevated levels of one or more anti-inflammatory or immunomodulatory molecules relative to a native populations of CD44.sup.+ cells. In some embodiments, the compositions, cell populations and pharmaceutical compositions and methods comprise a population of CD44.sup.+ cells modified ex vivo via a treatment that is effective to target cells to sites of inflammation.

Disclosed herein are methods of gene editing, or endogenous suppression, of cytokines/chemokines/transcription factors secreted from chimeric antigen receptor (CAR)-bearing immune effector cell such as CAR-T cells for the mitigation of cytokine release syndrome and/or CAR-T associated neuropathy. These methods involve insertion of the CAR into a locus of a cytokine gene, blocking its expression. Also disclosed herein are (CAR)-bearing immune effector cells with CARs inserted into a locus of a cytokine gene, and methods of treatment of diseases with immunotherapy with a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy.

Provided are recombinant cytokine receptors that comprise an IL-2 intracellular domain and an extracellular domain that binds to a cytokine other than IL-2. Also provided herein are Treg cell comprising recombinant cytokine receptors and methods of use.

The invention includes compositions comprising at least one chimeric alloantigen receptor (CALLAR) specific for an alloantibody, vectors comprising the same, compositions comprising CALLAR vectors packaged in viral particles, and recombinant T cells comprising the CALLAR. The invention also includes methods of making a genetically modified T cell expressing a CALLAR, wherein the expressed CALLAR comprises a Factor VIII or fragment thereof extracellular domain.

The present disclosure provides the use of fratricide-resistant chimeric antigen receptor T (CAR-T) cells targeting antigens expressed by T cell malignancies.

The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR chain, TCR chain, beta-2 microglobulin, a HLA molecule, CTLA-4, PD1, and FAS and further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

Provided herein are populations of ex vivo expanded umbilical cord blood-derived regulatory T cells. Also provided are methods of making and using the same.