The present disclosure relates to methods related to the treatment of IgA nephropathy. More specifically, the present disclosure relates to methods for treating a patient having IgA nephropathy (IgAN), to methods for reducing the serum Gd-IgA1 level in a patient having IgA nephropathy (IgAN), to methods for reducing the proteinuria in a patient having IgA nephropathy, to methods for reducing the serum Gd-IgA1 level and the proteinuria in a patient having IgA nephropathy, and further related disclosure.

The present invention relates to new CD22 Chimeric Antigen Receptors (CD22 CAR), an engineered immune cell endowed with said new CD22 CAR and comprising at least inactivated TRAC gene for use in therapy. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.

Some embodiments provided herein are chimeric costimulatory antigen receptor (CoStAR), useful in adoptive cell therapy (ACT), and cells comprising the CoStAR. In some embodiments, the CoStAR can act as a modulator of cellular activity enhancing responses to defined antigens. In some embodiments, CoStAR and/or fusion proteins, nucleic acids encoding the CoStAR and therapeutic uses thereof are also provided.

Several embodiments disclosed herein relate to the compositions comprising engineered Natural Killer (NK) cells that express a chimeric receptor, the chimeric receptor imparting to the NK cells an enhanced ability to target specific cells, such as cancerous cells or those affected by an infectious disease. Several embodiments relate to NK cells that target cells expressing natural ligands of NKG2D, where the NK cells comprise transmembrane and/or signaling domains that lead to cytotoxic and/or cytolytic effects when the NK cells bind a target cell. Uses of NK cell compositions to treat diseases are also provided for in several embodiments.

Provided herein are compositions and methods for the treatment of a disease, such as cancer, using a chimeric antigen receptor or genetically-modified cells comprising a chimeric antigen receptor having specificity for CD20. The invention provides polynucleotides encoding such chimeric antigen receptors, and genetically-modified cells comprising such chimeric antigen receptors. Also provided are methods for making such genetically-modified cells and pharmaceutical compositions comprising the same. The invention further provides methods for treating a disease (e.g., cancer) in a subject by administering such genetically-modified cells or compositions. The main embodiments concern CARs with an scFv specific for CD20, the hinge and transmembrane domains from CD8, the costimulatory cytoplasmic or signalling domain from co-stimulatory molecules Novell (N1) or Novel6 (N6) and the CD3zeta intracellular signaling domain.

The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward tumor and pathogen antigens. It relates to immunoresponsive cells comprising two or more chimeric antigen receptors (CARs), wherein the CARs comprise different intracellular signaling domains, in particular, the intracellular signaling domains of the CARs comprise different co-stimulatory molecules.

The present disclosure provides fusion proteins with improved signaling properties. Disclosed embodiments include fusion proteins that comprise an extracellular component comprising a target-binding domain, a transmembrane domain, and an intracellular component comprising a SH2 domain or a functional portion or variant thereof, and have improved signaling in response to antigen-binding, including of solid-tumor antigens with low levels of expression. Recombinant host cells expressing the fusion proteins, and polynucleotides encoding the fusion proteins, are also provided, as are compositions and methods comprising the same.

Provided are a B-cell antibody receptor (BAR), a BAR-T cell and others which are effective for the treatment of diseases associated with antibodies produced in the bodies of patients. The B-cell antibody receptor (BAR) according to the present invention comprises (a) an antibody binding domain, (b) a transmembrane domain, (c) an intracellular domain of a costimulating factor and (d) an intracellular domain of an activated receptor which are linked together.

The subject invention pertains to a chimeric antigen receptor, a T cell comprising said CAR and methods of making and using said CAR and said T cell for the treatment of a cancer and/or an immune disease. In specific embodiments, the method comprises the use of T cells comprising CARs to target different antigens on target cells. In further specific embodiments, the CARs of the invention comprise NS3 protease domains and cleavage sites, which NS3 domains are inhibited by small molecule inhibitors for customized CAR-T cell therapy.

As a technique enabling to simply and accurately diagnose human T cell leukemia virus type 1 (HTLV-1) related disease, there is provided a diagnostic method for an HTLV-1 related disease based on an amount of tumor necrosis factor receptor 2 (TNFR2) in a blood sample taken from a subject, wherein (1) it is determined based on an increase of the amount of TNFR2 that the subject suffers from, or is likely to develop, the HTLV-1 related disease; and/or (2) it is determined based on a decrease of the amount of TNFR2 that the subject is in remission, or is likely to be in remission, of the HTLV-1 related disease.