Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

Immunotherapies, particularly chimeric antigen receptors targeting IL-13R?2 and their use for treating cancer are provided. A single chain fragment variable (scFv) that specifically binds IL-13R?2, chimeric antigen receptors (CARs) including the IL-13R?2 scFv, nucleic acids encoding the CARs, vectors including the nucleic acids encoding the CARs, and immune cells expressing the CARs are provided. Also provided are methods of treating a subject with cancer, including administering to the subject an immune cell expressing an IL-13R?2 scFv-CAR alone or in combination with 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 provides recombinant TIM-4 fusion proteins comprising an extracellular domain of TIM-4 and at least one co-stimulatory domain. Also provided are cells comprising the fusion protein and methods of making and using the same.

The present disclosure provides an immune cell genetically modified to produce two antigentriggered polypeptides, each recognizing a different cell surface antigen. The present disclosure provides a system two antigen-triggered polypeptides, each recognizing a different cell surface antigen. The present disclosure provides a method of killing a target cancer cell, using a genetically modified immune cell or a system of the present disclosure. The present disclosure provides a computational method to identify target antigen pairs on a cancer cell.

The invention relates to therapy and methods of applying the therapy to a patient. The invention includes the introduction of immature dendritic cells into the patient and the introduction of anti-TNF antibody into the patient. The immature dendritic cells are introduced intratumorally and/or through vessel and the anti-TNF antibody is introduced intratumorally and/or through vessel and/or subcutaneously. The immature dendritic cells can be formed by collecting monocyte cells from the patient and culturing the cells in a culture medium. The invention can be effective to regress, reduce or eliminate tumor cells in tumor tissue of the patients, including metastasized tumors. Further, the treatment of the invention is effective in the absence of conventional therapy, such as radiotherapy and chemotherapy.

Provided herein is a composition comprising, a cell, comprising nucleic acids encoding a chimeric antigen receptor (CAR) and one or more of signaling proteins selected from K13-vFLIP, MC159-vFLIP, cFLIP-L, cFLIP-p22, HTLV1-Tax and HTLV2-Tax, wherein the CAR comprises an a) extracellular antigen specific domain, b) a transmembrane domain and c) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM); wherein c) is located at the C-terminus of the chimeric receptor. In some embodiments, the CAR further comprises one or more co-stimulatory domains. Also provided herein are methods for treating diseases using the compositions described herein.

Provided provided herein are methods of treating a subject having a brain tumor, e.g., a glioblastoma by administering to the subject an effective amount of a cell population comprising human placenta-derived natural killer cells. Also provided are methods of suppressing the growth of brain tumor cells comprising contacting the glioblastoma cells with an effective amount of a cell population comprising human placenta-derived natural killer cells. Further provided are compositions comprising subject an effective amount of a cell population comprising human placenta-derived natural killer cells for use in the treatment of a brain tumor in a subject or for use in the manufacture of a medicament for treatment of a brain tumor in a subject.

The invention provides compositions and methods for treating diseases associated with expression of EGFRvIII. The invention also relates to chimeric antigen receptor (CAR) specific to EGFRvIII, vectors encoding the same, and recombinant T cells comprising the anti-EGFRvIII CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an anti-EGFRvIII binding domain.

The novel synergistic combination of immune checkpoint blockade and hematopoietic stem cell transplantation and/or hematopoictic stem cell mobilization yield synergistic effects in disease therapy.