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.

This disclosure relates to chimeric antigen receptors targeting T cell malignancies. The present disclosure also relates to the development of methods for inactivation with engineered CARs, to enhance T cell functions or reduce T cell suppression.

The present invention describes a method for treating cancer comprising adoptive transfer of tumor antigen specific CD8+ T cells and an oncolytic virus vaccine targeting the same antigen.

The disclosure provides cells comprising CD19-directed chimeric antigen receptor (CAR) genetically modified autologous T cell immunotherapy for the treatment of, e.g., relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Some aspects of the disclosure relate to methods of treatment and monitoring following infusion of T cell therapy provided herein.

Provided here, amongst other things, are populations of expanded and stimulated natural killer cells, pharmaceutical compositions comprising populations of expanded and stimulated natural killer cells, and methods of expanding and stimulating natural killer cells

Provided are single domain antibodies that bind to GUCY2C, and chimeric antigen receptors comprising same. Further provided are engineered immune effector cells (such as T cells) comprising the chimeric antigen receptors. Pharmaceutical compositions, kits and methods of treating a disease or disorder are also provided.

Modulators of syndecan-2, such as an antibody to syndecan-2 that cross-links syndecan-2 on the cell surface or a syndiecan-2 polypeptide that interferes with syndecan-2 receptor binding, is used to regulate a Th17 mediated disease such as an autoimmune disease, fibrosis or cancer.

Chimeric antigen receptors containing tumor necrosis factor receptor superfamily member transmembrane domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

The novel synergistic combination of immune checkpoint blockade and hematopoietic stem cell transplantation and/or hematopoietic stem cell mobilization yield synergistic effects in disease therapy.

Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.