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.

The present disclosure generally relates to, among other things, a new class of receptors engineered to modulate transcriptional regulation in a ligand-dependent manner. In particular, the new receptors contain a heterologous stop-transfer-sequence and a ?-secretase cleavable transmembrane domain. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various diseases such as cancers.

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 reactive to a first antigen and at least one endogenous secreted immunoglobulin reactive 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 methods and compositions useful for treating autoimmune diseases and disorders. For example, the disclosure demonstrates that hypergammaglobulinemia and subsequent accelerated kidney disease can be suppressed by Ig minigene-induced CD8.sup.+ T cells that make CD4.sup.+T cells hyporesponsive to antigenic stimulation, thus causing inhibition of renal disease and subsequent increased survival.

The present invention relates to a distinct B cell subset, B10 cells, that regulate T cell mediated inflammatory responses through the secretion of interleukin-10 (IL-10). The invention also relates to the use of B10 cells in the manipulation of immune and inflammatory responses, and in the treatment of disease. Therapeutic approaches involving adoptive transfer of B10 cells, or expansion of their endogenous levels for controlling autoimmune or inflammatory diseases and conditions are described. Ablation of B10 cells, or inhibition of their IL-10 production can be used to upregulate immunodeficient conditions, ameliorate infectious diseases and/or to treat tumors/cancer. Diagnostic applications are also encompassed.

Provided herein are methods, kits and compositions for the treatment and/or prevention of ovarian cancer through the induction of an immune response against Anti-Mullerian Hormone Receptor, Type II (AMHR2).

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 reactive to a first antigen and at least one endogenous secreted immunoglobulin reactive 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.

A vaccine composition is described that is composed of 3 cells lines, the U266, H929, and K562. Methods are described for using the vaccine composition in methods of immunizing against plasma cell disorders, including multiple myeloma and related disorders.

The present invention relates to genetically modified B cells and their uses thereof, for example, for the treatment of a variety of diseases and disorders, including cancer, heart disease, inflammatory disease, muscle wasting disease, neurological disease, and the like. In certain embodiments, the invention relates to an isolated modified B cell (CAR-B cell), capable of expressing a chimeric receptor (CAR-B receptor), wherein said chimeric receptor comprises (a) an extracellular domain; (b) a transmembrane domain; and (c) a cytoplasmic domain that comprises at least one signaling domain. In various embodiments, the invention comprises an isolated modified B cell, wherein said B cell is capable of expressing and secreting a payload, wherein the payload is not naturally expressed in a B cell or is expressed at higher levels than is naturally expressed in a B cell. In various embodiments, the payload is an antibody or fragment thereof.

The present application provides peripheral blood mononuclear cells comprising an antigen, methods of manufacturing such PBMCs, and methods of using such PBMCs, such as for modulating an immune response in an individual. In some embodiments, the PBMCs are conditioned by incubating the PBMC in the presence of an adjuvant.