The present invention provides a chimeric antigen receptor (CAR) that recognizes B7-H3 (CD276), as well as methods of use in the treatment of diseases and disorders.

The present invention relates to a polypeptide comprising (a) a first set of six complementarity determining regions (CDRs) configured to bind a first antigen; and (b) (ba) a second set of six CDRs configured to bind a second antigen; or (bb) a ligand capable of binding to a second antigen; wherein (i) said first antigen is selected from Hepatitis B virus (HBV) small surface antigen; HBV medium surface antigen; and HBV large surface antigen; and (ii) said second antigen is selected from surface antigens presented by immune effector cells such as natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Also provided are compositions for use in a method of treating or preventing HBV infection and/or a condition caused by said HBV infection, said condition caused by said HBV infection being selected from liver cirrhosis and hepatocellular carcinoma.

Disclosed herein are methods and compositions for inactivating TCR and/or HLA genes, using engineered nucleases comprising at least one DNA binding domain and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided.

Contemplated immunotherapies include co-administration of an activated NK cell that is further genetically modified and a cancer therapeutic agent. In preferred embodiments, activated NK cells are further modified to taNK cells, which include a chimeric antigen receptor (CAR) with affinity for a cancer specific antigen, a cancer associated antigen, or a tumor specific antigen. Activated NK cells can also be further genetically modified to include high affinity Fc receptor CD16a (V158). Appropriate cancer therapeutic agents include chemotherapeutic drugs (e.g., nant-paclitaxel) or cancer targeted antibodies (e.g., trastuzumab).

The presently disclosed subject matter provides for methods and compositions for treating multiple myeloma. It relates to chimeric antigen receptors (CARs) that specifically target B cell maturation antigen (BMCA), and immunoresponsive cells comprising such CARs. The presently disclosed BMCA-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

Disclosed herein is a vaccine comprising an antigen and IL-33. Also disclosed herein is a method for increasing an immune response in a subject in need thereof. Further disclosed herein is a method for treating cancer in a subject in need thereof. The methods may comprise administering the vaccine to the subject.

Disclosed herein are cells that are immunoinhibitory cell, which cells recombinantly express a dominant negative form of an inhibitor of a cell-mediated immune response of the cell. In certain embodiments, the immunoinhibitory cell is a regulatory T cell. In another aspect, provided herein is a regulatory T cell that recombinantly expresses a dominant negative form of an inhibitor of a regulatory T cell-mediated immune response. The cells can be sensitized to an antigen that is the target of a pathologic immune response associated with an immune-mediated disorder. Additionally provided are methods of using such cells to treat an immune-mediated disorder in a subject in need thereof.

The present disclosure provides compositions and methods for targeting a minor histocompatibility (H) antigen (HA-1.sup.H) to, for example, prevent or manage relapse of a hematological malignancy after allogeneic hematopoietic stem cell transplantation (HCT). Also provided are transgene constructs encoding engineered binding proteins, such as a T cell receptor or a chimeric antigen receptor, optionally encoding additional components such as a co-receptor and/or safety switch. Such transgene constructs can be transduced into an immune cell, such as a T cell, and used as an immunotherapy in a subject having a hematological malignancy or at risk for recurrence of the hematological malignancy (e.g., leukemia, lymphoma, myeloma).

Provided herein are polynucleotides encoding chimeric antigen receptors (CARs) comprising a CD19 antigen binding domain that specifically birnds to CD19 and is resistant to rituximab binding; and immune cells comprising these CD19-specific CARs, e.g., CAR-T cells. Also provided are methods of making and using these CD19-specific CARs, and immune cells comprising these CD19-specific CARs.

The present invention relates to: a composition and a kit for preventing, alleviating or treating atopic dermatitis, comprising primed function-enhanced stem cells and regulatory T cells; and a method for preventing, alleviating or treating atopic dermatitis by using same. When function-enhanced stem cells, of the present invention, treated with TNF-?, IFN-? and IFN-? or TNF-?, IFN-?, IFN-? and vitamins are treated in combination with regulatory T cells, the imbalance of Th1/Th2 cells of an atopic dermatitis patient can be alleviated and the status of the atopic dermatitis patient can be shifted to Th1, and thus the present invention can be widely used in various fields of prevention, alleviation or treatment of atopic dermatitis.