The present invention contemplates that complement receptor 1 and 2 may play a role in the induction of regulatory B cells under inflammatory conditions that accompany immune mediated diseases. For example, long noncoding RNA may regulate transcription of the complement receptor I gene, thereby resulting in an induction and/or suppression of regulatory B cells. Such long noncoding RNA in mature B cells may be specifically targeted to modify 10 complement receptor 1 levels and induce or suppress the generation of antigen-specific regulatory B cells, thereby modifying the course of immune mediated diseases including, but not limited to, autoimmune disease, cancer, and infection.

Down-regulating autoimmune regulator (AIRE) function in B cells to produce antibodies is described. The antibodies can be class-switched, high affinity, and neutralizing, and have a high degree of somatic hypermutations, even in the framework region, as compared to antibodies produced in the absence of AIRE downregulation.

The technology described herein relates, at least in part, to compositions comprising and methods for isolating and enriching natural IgM-producing phagocytic B (NIMPAB) cells and methods of producing IgM antibodies using such cells, as well as uses of the antibodies produced by the methods for the prevention and treatment of diseases wherein immunotherapy with such natural IgM antibodies and their derivatives can be useful.

Recombinant expression of CXADR in a cell, and especially an immune competent cell is employed to enable or improve gene delivery to the cell by an adenovirus. In particularly preferred aspects, the immune competent cell is a an NK cell, a T-cell, a B-cell, a macrophage, or a dendritic cell, and the gene delivery comprises a recombinant nucleic acid encoding a disease-specific antigen, such as a patient specific neoepitope or a tumor associated antigen.

In certain embodiments, this disclosure relates to conjugates comprising a polypeptide of GM-CSF and a polypeptide IL-4. Typically, the GM-CSF and IL-4 are connected by a linker, e.g., polypeptide. In certain embodiments, the disclosure relates to isolated nucleic acids encoding these polypeptide conjugates, vectors comprising nucleic acid encoding polypeptide conjugates, and protein expression systems comprising these vectors such as infectious viral particles and host cells comprising such nucleic acids.

Disclosed are biocompatible core/shell compositions suitable for the delivery of populations of mRNA molecules to mammalian cells. The disclosed core-shell structured multicomponent compositions are optimized for the delivery of mRNAs encoding one or more cancer- or tumor-specific antigens to a population of antigen presenting cells, including, for example, human dendritic cells, macrophages and B cells. Also disclosed are methods for use of these compositions as therapeutic cancer vaccines.

Down-regulating autoimmune regulator (AIRE) function in B cells to produce antibodies is described. The antibodies can be class-switched, high affinity, and neutralizing, and have a high degree of somatic hypermutations, even in the framework region, as compared to antibodies produced in the absence of AIRE downregulation.

A method for regenerating a humoral immunity system. A pluripotent stem cell is used for expressing a RUNX1 gene, a HOXA9 gene and an LHX2 gene to efficiently obtain B cell seeds after in vitro induction differentiation, and after transplantation, a complete humoral immune system can be reconstructed in an animal in which the humoral immune system is missing. According to the method, an antigen-specific antibody immune response can be realized, a specific high-affinity antibody can be generated against an antigen, and immunological memory can be produced. Meanwhile, the reconstructed immune system is safe, and carries no risk of tumorigenicity.

The present invention relates to combination therapies with anti-CD38 antibodies.

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.