Provided herein are methods, compositions and uses involving immunotherapies, such as adoptive cell therapy, e.g., T cell therapy, and inhibitors of a TEK family kinase, such as BTK or ITK. The provided methods, compositions and uses include those for combination therapies involving the administration or use of one or more such inhibitor in conjunction with another agent, such as an immunotherapeutic agent targeting T cells, such as a therapeutic antibody, e.g., a multispecific (e.g., T cell engaging) antibody, and/or genetically engineered T cells, such as chimeric antigen receptor (CAR)-expressing T cells. Also provided are methods of manufacturing engineered T cells, compositions, methods of administration to subjects, nucleic acids, articles of manufacture and kits for use in the methods. In some aspects, features of the methods and cells provide for increased or improved activity, efficacy, persistence, expansion and/or proliferation of T cells for adoptive cell therapy or endogenous T cells recruited by immunotherapeutic agents.

Provided are chimeric VEGF-binding proteins and nucleic acids (e.g., a vector) encoding chimeric VEGF-binding proteins, methods and host cells for producing these proteins and nucleic acids, and pharmaceutical compositions containing these proteins and nucleic acids. Also provided are methods of treating an angiogenic disease or disorder that include administering at least one of the chimeric VEGF-binding proteins or at least one of the nucleic acids (e.g., a vector) encoding a chimeric VEGF-binding protein.

The present invention concerns methods and compositions for immunotherapy employing a modified T cell comprising disrupted T cell receptor and/or HLA and comprising a chimeric antigen receptor. In certain embodiments, the compositions are employed allogeneically as universal reagents for off-the-shelf treatment of medical conditions such as cancer, autoimmunity, and infection. In particular embodiments, the T cell receptor-negative and/or HLA-negative T cells are generated using zinc finger nucleases, for example.

The present invention provides a complex for use in the prevention and/or treatment of cancer, the complex comprising a) a cell penetrating peptide, b) at least one antigen or antigenic epitope, and c) at least one TLR peptide agonist, wherein the components a)-c) are covalently linked. In particular, compositions for use in the prevention and/or treatment of cancer, such as a pharmaceutical compositions and vaccines are provided.

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.

The present invention relates to the field of adoptive immunotherapy. The invention provides methods for generating phenotypically defined, functional, and/or expandable T cells from pluripotent stem cells engineered through safe genetic modifications. The engineered cells may provide one or more of: 1) targeting a specific predetermined antigen expressed on the cell surface of a target cell in an HLA independent manner, 2) enhanced survival and functional potential 3) off-the-shelf T cells for administration to multiple recipients, eventually across immunogenic barriers, and/or 4) cytotoxic potential and anti-tumor activity.

Generation and identification of highly effective immune effector cell in terms of target cell-killing activity can be enhanced by optimizing the proximity between a target cell and the immune effector cell. The cancer-killing T cells described herein can provide highly effective therapies for diverse cancer types, e.g., solid cancers, hematological cancers, and metastatic forms thereof. Provided herein are ex-vivo methods of generating cancer-killing T cells, compositions comprising such immune cells; methods of using the cells, methods of selecting optimal agents for enhancing the target cell killing activity, methods of selecting an optimized immune cell and methods of using this approach to evaluate patient responsiveness to other cancer therapies.

The present invention relates to a method for producing a DNA vaccine for cancer immunotherapy comprising at least the steps of (a) transforming an attenuated strain of Salmonella with at least one DNA molecule comprising at least one expression cassette encoding at least one antigen or at least one fragment thereof; (b) characterizing at least one transformed cell clone obtained in step (a); and (c) selecting at least one of the transformed cell clone(s) characterized in step (b) and further characterizing said at least one selected transformed cell clone. The present invention further relates to a DNA vaccine obtainable by the method according to the present invention.

The present disclosure provides novel cell compositions engineered to express at least a chimeric antigen receptor and a survival factor. Methods of using such cell compositions are also described.

Provided are chimeric VEGF-binding proteins and nucleic acids (e.g., a vector) encoding chimeric VEGF-binding proteins, methods and host cells for producing these proteins and nucleic acids, and pharmaceutical compositions containing these proteins and nucleic acids. Also provided are methods of treating an angiogenic disease or disorder that include administering at least one of the chimeric VEGF-binding proteins or at least one of the nucleic acids (e.g., a vector) encoding a chimeric VEGF-binding protein.