Memorial Sloan Kettering Cancer Center

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Prasad S Adusumilli

Michel Sadelain

Dimiter Stanchev Dimitrov

Yang Feng

Yuman Fong

Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.

Immune cell compositions and methods of use

Disclosed herein are cells that are immune cells, which cells recombinantly express a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, and optionally recombinantly express a chimeric antigen receptor (CAR), wherein the CAR binds to a viral antigen. In certain embodiments, the immune cell is an immunostimulatory cell, such as a T cell. In certain embodiments, the immune cell is an immunoinhibitory cell, such as a regulatory T cell. Also disclosed herein are immune cells that recognize and are sensitized to a viral antigen, which immune cells recombinantly express a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell. The cells can be sensitized to an antigen that is a viral antigen. Additionally provided are methods of using such cells to treat a viral infection in a subject in need thereof.

Immune cell compositions and methods of use for treating viral and other infections

The presently disclosed subject matter provides for methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to chimeric antigen receptors (CARs) that specifically target human mesothelin, and immunoresponsive cells comprising such CARs. The presently disclosed mesothelin-targeted CARs have enhanced immune-activating properties, including anti-tumor activity.

Method of reducing mesothelin-expressing tumor burden by administration of T cells comprising mesothelin-targeted chimeric antigen receptors

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.

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New York, NY, United States of America

Prasad S Adusumilli