Provided is directed to the field of immunotherapy. Specifically, provided are compositions and methods for improved T cell modulation ex vivo and in vivo and for the treatment of cancer and other pathologies. More specifically, embodiments of the subject matter are directed to the use of soluble NTB-A polypeptides or agonists thereof for the treatment of cancer patients, for preventing and treating cytopenia in susceptible patients, and for the ex vivo preparation of improved cell compositions.

Provided by the disclosure are methods for modulating differentiation of regulatory T cells (e.g., CD4.sup.+ or CD8.sup.+ regulatory T cells). In some embodiments, methods include contacting regulatory T cells with an agent that decreases Helios activity and/or Helios expression.

Disclosed are compositions and methods for ex vivo expansion of tumor-infiltrating lymphocytes for use in adoptive cell therapy (ACT). Also disclosed are compositions and method for identifying an agent for ex vivo expansion of tumor-infiltrating lymphocytes for use in ACT. Also disclosed are methods for treating cancer using tumor-infiltrating lymphocytes expanded by the disclosed methods.

The presently disclosed subject matter relates to immunoswitch particles that switch off immunosuppressive pathways on tumor cells or immunosuppressive molecules induced by tumor cells in the tumor microenvironment, or virus infected cells or immunosuppressive molecules induced by virus infected cells in the microenvironment surrounding the virus infected cells, while simultaneously switching on co-stimulatory or co-inhibitory pathways on T cells, as well as method for converting immunosuppressive infections.

This document provides methods and materials for treating cancer. For example, methods and materials for identifying antigens and combinations of antigens that can be used to treat cancer as well as combinations of antigens having the ability to reduce established tumors (e.g., gliomas) within a mammal (e.g., a human) are provided.

The present invention relates to a human macrophage for use in cancer therapy, said human macrophage comprising at least one mutation in both alleles of a chromosomal gene, wherein said macrophage is resistant to tumor-induced reprogramming and/or shows anti-tumor activity. The human macrophage of the invention demonstrates typical markers of an M1 macrophage, such as the presence of MHC class II proteins, even after having been cultured in an environment which promotes M2-polarization, such as in the presence of M-CSF and/or IL4 and/or IL13. The invention also relates to a collection of human macrophages of the invention, to their use in medicine, and in particular to their use in cancer therapy such as the treatment of solid tumors as a preferred example.

Provided are modified tumor-infiltrating lymphocyte and the use thereof, in particular provided is a method for culturing the tumor-infiltrating lymphocyte (TIL), which comprises increasing the expression and/or enhancing the activity of at least one cytokine of the TIL. Also provided is a method for preventing and/or treating tumors by using the tumor-infiltrating lymphocyte.

The present disclosure provides methods for selecting donors for ??T cell-based immunotherapy. The disclosure also provides methods for expanding and activating ?? T cells with improved cytotoxicity toward tumor cells and reduced T cell exhaustion. Pharmaceutical compositions comprising the expanded ?? T cells and methods of treatment are also provided.

The present invention discloses humanized monoclonal antibodies that specifically bind to STn carbohydrate antigen with high specificity and selectivity, functional fragments of the humanized monoclonal antibodies such as scFv, conjugates and chimeric antigen receptors comprising the humanized monoclonal antibodies or the fragment thereof such as scFv. The invention further provides cells and compositions comprising the antibodies, fragments thereof or CARs as well as their use in diagnostics and treatment of cancer.

The present disclosure provides transgenic T cells expressing engineered dimeric antigen receptors (DARs) that bind GD2. where the DAR includes a heavy chain binding region on one polypeptide chain and a light chain binding region on a separate polypeptide chain. The two polypeptide chains that make up the dimeric antigen receptors can dimerize to form an antigen binding domain. The transgenic T cells can be used for directed cell therapy.