As described below, the present invention features methods for enhancing the efficacy of a tumor antigen in inducing an anti-cancer immune response in a subject by administering an OX40 agonist and an Indoleamine 2,3-dioxygenase (IDO) inhibitor with the tumor antigen.

The present invention provides methods and compositions related to multivalent carbohydrate antigen structures comprising cancer or infection associated ganglioside carbohydrate antigens. Said carbohydrate structures may be used to induce immunity against said carbohydrate antigens. In some embodiments, carbohydrate structures may be administered to a subject thereby inducing immunity in the subject, for example, the administration of a vaccine comprising said carbohydrate structure. Also provided are methods to induce an immune response in a subject in need thereof by administering said carbohydrate structure. Further provided are methods of producing an antibody or TCR that bind said carbohydrate antigens.

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.

The invention describes vaccine compositions combined in the same proportion with the extracellular domains of growth factor receptors Her1 and Her2 or fragments thereof and furthermore very small size proteoliposomes derived from proteins of the outer membrane of Neisseria meningitidis and GM3 ganglioside (VSSP-GM3), administered subcutaneously. The disclosed compositions, which induce the production of antibodies are used for the treatment of malignancies and offer advantages because they completely remove the tumor mass thus preventing tumor regression due to the emergence of resistant variants.

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 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 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.

The present invention comprises compositions, methods, and devices for enhancing an endogenous immune response against a cancer. Devices and methods provide therapeutic immunity to subjects against cancer.