Abstract: The present disclosure provides chimeric cytokine receptors comprising an intracellular signaling domain of an interleukin-9 receptor alpha (IL9Ra). The present disclosure also provides modified cell(s), i.e., immune cell(s) or precursor cell(s) thereof, wherein the cell(s) are engineered to express a) interleukin-9 receptor alpha (IL9Ra), or a chimeric cytokine receptor disclosed herein; and b) a chimeric antigen receptor (CAR). The present disclosure further provides a vector (e.g., an oncolytic adenoviral vector) comprising a nucleic acid sequence encoding a cytokine, as well as methods of using the modified cells and the vector for treating cancer in a subject in need thereof. Also provided are modified immune cell(s) or precursor cell(s) thereof which are engineered to express a chimeric antigen receptor (CAR), wherein expression of Cullin 5 in the cell(s) is reduced and/or eliminated. Also provided are methods and uses of the modified cells, e.g., for treating at least one sign and/or symptom of cancer.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention relates to targeting the stromal cell population in a tumor microenvironment. For example, in one embodiment, the invention provides a composition that is targeted to fibroblast activation protein (FAP). The invention includes a chimeric antigen receptor (CAR) which comprises an anti-FAP domain, a transmembrane domain, and a CD3zeta signaling domain.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.

Abstract: The present invention provides compositions and methods for inducing a CAR mediated trans-signal in a T cell. The trans-signaling CAR T cells comprise a first CAR having a first signaling module and a second CAR having a distinct second signaling module. The present invention also provides cells comprising a plurality of types of CARs, wherein the plurality of types of CARs participate in trans-signaling to induce T cell activation.

Abstract: The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.

Abstract: The present invention relates generally to the treatment of PML by infusion of activated and expanded autologous lymphocytes.

Abstract: The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an intracellular signaling molecule in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.

Abstract: The invention provides compositions and methods improved CAR T cell therapies. Specifically, the invention provides cells with reduced Tet, e.g., Tet2 function or expression, and methods of use therefore. The invention further provides Tet2 inhibitors and methods of use therefore in connection with CAR T cells.

Abstract: The present invention includes a method for expanding a population of electroporated T cells. The method includes electroporating a population of cells comprising T cells with mRNA encoding a chimeric membrane protein comprising an antigen binding domain to a molecule and an intracellular domain of a co-stimulatory molecule, wherein the cultured T cells expand at least 10 fold. The invention further includes an expanded population of T cells, compositions comprising the cells and methods of treatment.

Abstract: The present disclosure provides a CAR comprising a tumor antigen binding domain, a transmembrane domain, and an intracellular domain comprising an intracellular signaling domain of an interleukin-9 receptor alpha (IL9Ra), and modified cell(s), i.e., immune cell(s) or precursor cell(s) thereof, engineered to express the CAR. Also provided are methods and uses of the modified cells, e.g., for treating at least one sign and/or symptom of cancer. Related nucleic acids, vectors, and pharmaceutical compositions are also provided.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of a tumor antigen as described herein. The invention also relates to nucleic acids comprising a truncated PGK promoter operably linked to a chimeric antigen receptor (CAR) specific to a tumor antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a tumor antigen as described herein.

Abstract: The present invention provides compositions and methods for inhibiting the depletion of healthy tissue during CAR T cell therapy. In another embodiment, the invention includes a drug-molecule conjugate which is administered to a subject receiving CAR T cell therapy, where the conjugate binds to the CAR resulting in internalization of the conjugate and inhibition of T cell activity and/or death of the T cell.

Abstract: The present invention provides compositions and methods for treating cancer in a patient. In one embodiment, the method comprises a first-line therapy comprising administering to a patient in need thereof a genetically modified T cell expressing a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain and monitoring the levels of cytokines in the patient post T cell infusion to determine the type of second-line of therapy appropriate for treating the patient as a consequence of the presence of the CART cell in the patient.

Abstract: The present invention relates to lipid nanoparticles (LNP) or compositions thereof for delivery of mRNA molecules encoding CAR, nucleic acid molecule, and/or therapeutic agents to selected targets, such as cells. Thus, in various aspects, the present invention also provides methods of preventing or treating diseases or disorders in a subject in need thereof using the said LNPs or compositions thereof.

Abstract: 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.

Abstract: The present invention provides compositions and methods for inducing a CAR mediated trans-signal in a T cell. The trans-signaling CAR T cells comprise a first CAR having a first signaling module and a second CAR having a distinct second signaling module. The present invention also provides cells comprising a plurality of types of CARs, wherein the plurality of types of CARs participate in trans-signaling to induce T cell activation.

Abstract: The present invention includes a method for expanding a population of electroporated T cells. The method includes electroporating a population of cells comprising T cells with mRNA encoding a chimeric membrane protein comprising an antigen binding domain to a molecule and an intracellular domain of a co-stimulatory molecule, wherein the cultured T cells expand at least 10 fold. The invention further includes an expanded population of T cells, compositions comprising the cells and methods of treatment.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of a tumor antigen as described herein. The invention also relates to nucleic acids comprising a truncated PGK promoter operably linked to a chimeric antigen receptor (CAR) specific to a tumor antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a tumor antigen as described herein.

Abstract: 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.