The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to immunoresponsive cells comprising antigen recognizing receptors (e.g., chimeric antigen receptors (CARs) or T cell receptors (TCRs)), and expressing increased level of IL-18. In certain embodiments, the engineered immunoresponsive cells are antigen-directed and resistant to immunosuppression and/or have enhanced immune-activating properties.

The present invention relates to the field of bioengineering, and in particular to a chimeric antigen receptor (CAR) expression vector and use thereof. The CAR expression vector comprising a polynucleotide encoding a CAR and full length or fragment of a polynucleotide encoding a granulocyte-macrophage colony-stimulating factor (GM-CSF). The CAR-GM-T cell constructed by the present invention is capable of expressing high-level GM-CSF, not only directly enhancing killing activity of the CAR-GM-T cell per se but also facilitating the infiltration of the CAR-GM-T cell into a solid tumor. The CAR-GM-T cell has a stronger immune modulation function compared to the conventional CAR-T cell and systematically triggers the endogenous anti-tumor immune response, thereby achieving superior therapeutic efficacy against a solid tumor.

The present disclosure provides ex vivo methods which employ modified cells of leukemic origin to enhance the efficacy of adoptive cell therapy.

The present invention provides improved and/or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy for the treatment of cancer with TILs in combination with CT-LA-4 and PD-1 inhibitors and/or PD-L1 inhibitors as described herein.

A composition and method of ex vivo producing natural killer (NK) cells expressing a chimeric antigen receptor (CAR) or a transgenic T cell receptor (tg-TCR) capable of binding HER2 is disclosed. The method comprising: (a) expanding a population of NK cells by a method comprising: (i) culturing the population of NK cells under conditions allowing for cell proliferation, wherein the conditions comprise providing an effective amount of nutrients, serum, IL-15 and nicotinamide; and (ii) supplementing the population of NK cells with an effective amount of fresh nutrients, serum, IL-15 and nicotinamide 5-10 days following step (i) to produce expanded NK cells; so as to obtain an ex vivo expanded population of NK cells, and (b) upregulating expression of a CAR or a tg-TCR capable of binding HER2 in the ex vivo expanded population of NK cells.

Provided are compositions and methods for treating diseases associated with expression of mesothelin. Also provided are a chimeric antigen receptor (CAR) specific to mesothelin, vectors encoding the same, and recombinant T cells comprising the mesothelin CAR. Further provided are methods of administering a genetically modified T cell expressing a CAR that comprises a mesothelin binding domain.

The technology relates in part to binding molecules that specifically bind to a polypeptide that is the Isoform 2 of mesotheiin, or that specifically bind to an antigenic determinant (epitope) of the isoform 2 of mesotheiin, or that specifically bind to polypeptides containing an antigenic determinant (epitope) of the isoform 2 of mesotheiin, chimeric PD1 receptors that bind to PD ligands such as PDLs, to polynucleotides including vectors that encode such binding molecules, to ceils presenting such binding molecules and to methods of making such cells, to humanized forms of the binding molecules, and to methods of using such binding molecules, such as for treating cancers (e.g., ovarian cancers and mesotheliomas), including cancers in which the Isoform 2 of mesotheiin is specifically expressed and/or upregulated relative to normal tissues.

The present disclosure provides methods of modulating regulatory T-cell activity and function.

The present invention relates to the field of medicine, specifically the field of treatment of cancer. More specifically, the invention relates to a method for the ex vivo production of a population of highly functional NK cells from CD34-positive cells, to a population of highly functional NK cells obtained and to the use of such population of highly functional NK cells for adoptive cell therapy.

The invention provides antibodies, and antigen-binding fragments thereof, that specifically bind to a polypeptide, or antigenic portion thereof, wherein the polypeptide is selected from a) MUC16 ectodomain polypeptide, b) MUC16 cytoplasmic domain polypeptide, and c) MUC16 extracellular domain polypeptide that contains a cysteine loop polypeptide. The invention's antibodies and compositions containing them are useful in diagnostic and therapeutic applications for diseases in which MUC16 is overexpressed, such as cancer.