The present disclosure provides for efficient ex vivo processes for generating B cell lineages from human induced pluripotent stem cells (iPSCs). Cells generated according to the disclosure in various embodiments are functional and/or more closely resemble the corresponding lineage isolated from peripheral blood or lymphoid organs. The present invention in some aspects provides isolated cells and cell compositions produced by the methods disclosed herein, as well as methods for cell therapy.

Some embodiments of the method and compositions provided herein relate to methods of preparing cells expressing bispecific T cell engagers (BTCEs), and the use of such cells in certain therapies. In some embodiments, the cells are B cells or B cell precursors.

Some embodiments of the method and compositions provided herein relate to methods of preparing cells expressing bispecific T cell engagers (BTCEs), and the use of such cells in certain therapies. In some embodiments, the cells are B cells or B cell precursors.

The present invention provides a recombinant immune cell and the preparation method, the gene regulation system and the use thereof. By reducing or eliminating the expression and/or biological functions thereof of the BCOR gene and the ZC3H12A gene, the persistence of the recombinant immune cell is enhanced. In some embodiments, the present invention obtains CAR-T cells with knockout of double genes ZC3H12A and BCOR by gene editing, which can persist in vivo, solving the technical problem of long-term effectiveness of CAR-T treatment. In some embodiments, the gene-edited CAR-T cells persist in vivo and can continuously secrete therapeutic biological molecules, achieving the purpose of long-term effectiveness of a single administration.

The present invention provides a recombinant immune cell and the preparation method, the gene regulation system and the use thereof. By reducing or eliminating the expression and/or biological functions thereof of the BCOR gene and the ZC3H12A gene, the persistence of the recombinant immune cell is enhanced. In some embodiments, the present invention obtains CAR-T cells with knockout of double genes ZC3H12A and BCOR by gene editing, which can persist in vivo, solving the technical problem of long-term effectiveness of CAR-T treatment. In some embodiments, the gene-edited CAR-T cells persist in vivo and can continuously secrete therapeutic biological molecules, achieving the purpose of long-term effectiveness of a single administration.

Provided is a chimeric antigen receptor targeting CLL1 and an application thereof. The chimeric antigen receptor targeting CLL1 comprises an antigen binding domain, a hinge region, a transmembrane domain and a signal transduction domain; the antigen binding domain is an anti-CLL1 antibody. The present application uses an anti-CLL1 antibody as the antigen binding domain to construct a chimeric antigen receptor molecule, the chimeric antigen receptor targeting CLL1 has specific targeting effect on CLL1 positive tumor cells, and immune cells expressing chimeric antigen receptor targeting CLL1 have a significant killing effect in vitro and in vivo, and secrete a large amount of cytokine IFN- after co-cultured with CLL1 positive tumor cells, which has a specific clearance effect on CLL1 positive tumor cells.

Provided is a chimeric antigen receptor targeting CLL1 and an application thereof. The chimeric antigen receptor targeting CLL1 comprises an antigen binding domain, a hinge region, a transmembrane domain and a signal transduction domain; the antigen binding domain is an anti-CLL1 antibody. The present application uses an anti-CLL1 antibody as the antigen binding domain to construct a chimeric antigen receptor molecule, the chimeric antigen receptor targeting CLL1 has specific targeting effect on CLL1 positive tumor cells, and immune cells expressing chimeric antigen receptor targeting CLL1 have a significant killing effect in vitro and in vivo, and secrete a large amount of cytokine IFN- after co-cultured with CLL1 positive tumor cells, which has a specific clearance effect on CLL1 positive tumor cells.

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.

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.

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.