Abstract: 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.

Abstract: 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.

Abstract: Provided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express a uPAR-specific chimeric antigen receptor. Also disclosed herein are methods for using the engineered immune cells of the present technology to treat or ameliorate the effects of cancer and senescence-associated pathologies (e.g., lung fibrosis, atherosclerosis, Alzheimer's disease, diabetes, liver fibrosis, chronic kidney disease, aging, or osteoarthritis) by selectively targeting senescent cells. Also provided herein are methods for detecting the senescent cell burden in a patient.

Abstract: The presently disclosed subject matter provides methods and compositions for treating myeloid disorders (e.g., acute myeloid leukemia (AML)). It relates to immunoresponsive cells bearing antigen recognizing receptors (e.g., chimeric antigen receptors (CARs)) targeting AML-specific antigens.

Abstract: The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). 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.

Abstract: 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.

Abstract: The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of T cell receptors (TCRs) and engineered immunoresponsive cells comprising the same. The novel TCR binds to an antigen in an HLA-independent manner. In certain embodiments, the novel TCR provides enhanced sensitivity for a target gene having a low expression level.

Abstract: The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of T cell receptors (TCRs) and engineered immunoresponsive cells comprising the same. The novel TCR binds to an antigen in an HLA-independent manner. In certain embodiments, the novel TCR provides enhanced sensitivity for a target gene having a low expression level.

Abstract: 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 a co-stimulatory ligand and methods of use therefore for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Abstract: The presently disclosed subject matter provides methods and compositions for treating myeloid disorders (e.g., acute myeloid leukemia (AML)). It relates to immunoresponsive cells bearing antigen recognizing receptors (e.g., chimeric antigen receptors (CARs)) targeting AML-specific antigens.

Abstract: The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., pancreatic cancer). It relates to antigen recognizing receptor (e.g., chimeric antigen receptors (CARs)) that specifically target Sialyl Lewis A (e.g., human Sialyl Lewis A), and immunoresponsive cells comprising such CARs. The presently disclosed Sialyl Lewis A-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

Abstract: The present disclosure provides methods and compositions for treating cancers and pathogens. It relates to an immunoresponsive cell comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR)), and expressing a secretable TRAIL polypeptide.

Abstract: 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 a co-stimulatory ligand and methods of use therefore for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Abstract: Disclosed herein are methods and compositions for radiosensitizing tumor in subjects receiving radiation therapy by administering a gene therapy construct that results in expression of a secretory radiosensitizing agent in tumor endothelium.

Abstract: The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of T cell receptors (TCRs) and engineered immunoresponsive cells comprising the same. The novel TCR binds to an antigen in an HLA-independent manner. In certain embodiments, the novel TCR provides enhanced sensitivity for a target gene having a low expression level.

Abstract: The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of T cell receptors (TCRs) and engineered immunoresponsive cells comprising the same. The novel TCR binds to an antigen in an HLA-independent manner. In certain embodiments, the novel TCR provides enhanced sensitivity for a target gene having a low expression level.

Abstract: The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., multiple myeloma). It relates to anti-CD56 antibodies, chimeric antigen receptors (CARs) that specifically target human CD56, and immunoresponsive cells comprising such CARs. The presently disclosed CD56-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

Abstract: 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.

Abstract: The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of chimeric antigen receptors (CARs) and engineered immunoresponsive cells comprising the same. The engineered immunoresponsive cells comprising the novel CARs are antigen-directed and have extended persistence without compromising function.

Abstract: The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.