The presently disclosed subject matter provides polypeptide compositions comprising a chimeric antigen receptor (CAR) that targets mesothelin; and a dominant negative form of programmed death 1 (PD-1 DN). Also provided are immunoresponsive cells comprising such polypeptide compositions and uses of the polypeptide compositions and immunoresponsive cells for treatment, e.g., for treating solid tumors.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen recognizing receptor and one of a chimeric costimulatory receptor. Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression.

The present invention relates to the field of gene editing and tumor immunotherapy. In particular, the invention relates to methods for preparing modified T cells, such as CAR-T cells, by gene editing, and modified T cells prepared by the methods and uses thereof.

The technology relates generally to the field of immunology and relates in part to methods for activating T cells and other cells resulting in an immune response against a target antigen. The technology also relates to costimulation of therapeutic cells that express chimeric antigen receptors that recognize target antigens using chimeric MyD88- and CD40-derived polypeptides. The technology further relates in part to therapeutic cells that express chimeric antigen receptors, wherein the chimeric antigen receptors have an endodomain that includes MyD88- and CD40-derived polypeptides, and methods for treating patients using the modified therapeutic cells.

The present invention relates to a chimeric antigen receptor and immune cells expressing same and, more specifically, to a chimeric antigen receptor and immune cells, preferably T cells, expressing same, the chimeric antigen receptor comprising: an anti-mesothelin antibody or a fragment thereof; a signal peptide of CD8a; a hinge of CD28 or CD8a; a transmembrane domain of CD28 or CD8a; and an intracellular signaling domain comprising intracellular signaling region sequences of CD28, 4-1BB, and CD3ζ. The chimeric antigen receptor and T cells expressing same according to the present invention can be effectively used for cancer treatment since the immune cells exhibit excellent anticancer activity.

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression.

The present invention concerns methods and compositions for immunotherapy employing a modified T cell comprising a chimeric antigen receptor (CAR). In particular aspects, CAR-expressing T-cells are producing using electroporation in conjunction with a transposon-based integration system to produce a population of CAR-expressing cells that require minimal ex vivo expansion or that can be directly administered to patients for disease (e.g., cancer) treatment.

Chimeric antigen receptors (CARs) and CAR-expressing T cells are provided that can specifically target cells that express an elevated level of a target antigen. Likewise, methods for specifically targeting cells that express elevated levels of antigen (e.g., cancer cells) with CAR T-cell therapies are provided.

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.