Mesenchymal stromal cells are engineered to express a chimeric antigen receptor (CAR), that specifically binds a marker of activated myeloid cells, including without limitation folate receptor beta; and are administered to an individual for treatment of inflammation at sites characterized by the presence of activated myeloid cells.

Compositions and methods for reducing MHC class II protein expression in a cell comprising genetically modifying CIITA for use e.g., in adoptive cell transfer therapies.

Chimeric antigen receptors (CARs) are provided that comprise a CD123-specific antigen recognition domain and IL7Ra transmembrane and intracellular signaling domains (CD123/IL7Ra CARs). In particular embodiments, provided herein are engineered lymphocytes that express and display CD123/IL7Ra CARs, and methods of targeting CD123-positive leukemic cells and treating leukemias, such as acute myeloid leukemia (AML), therewith.

Provided herein are T-cell receptor (TCR) fusion proteins (TFPs) having specificity for one or more tumor cell associated antigens, T cells engineered to express one or more TFP, and methods of use thereof for the treatment of diseases, including cancer.

Disclosed herein are chimeric antigen receptor (CAR) polypeptides that can be used with adoptive cell transfer to target and kill TAG-72-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a TAG-72-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

The present invention pertains to novel modulators of resistance against T-cell mediated cytotoxic immune responses. The invention provides antagonists of immune escape mechanisms and therefore offers a novel approach for treating, or aiding a treatment, of various proliferative diseases such as cancerous diseases, in particular melanoma, pancreatic cancer and colorectal cancer. The invention specifically discloses the receptor Olfactory Receptor, Family 10, Subfamily H, Member 1 (OR10H1)as a checkpoint molecule in tumor resistance against cytotoxic T-cells. Provided is the inhibition of OR10H1 expression and/or function as a strategy for enhancing tumor susceptibility to a patients T-cell mediated immune response. Provided are antigen binding constructs for the detection of the OR10H1 protein, as well as inhibitory compounds, such as siRNA/shRNA molecules targeting OR10H1 and anti-OR10H1 antibodies, forimpairing the immune escape mediated by OR10H1. The invention furthermore provides screening methods for the identification of novel cancer therapeutics based on the modulation OR10H1 expression/function, diagnostic methods for the detection of immune resistance of a tumor to cytotoxic T-cell responses, as well as pharmaceutical compositions and diagnostic kits for performing these methods.

Provided are a polypeptide and nucleic acid for encoding the polypeptide, a nucleic-acid construct, an expression vector, and a host cell containing the nucleic acid, an antigen-presenting cell presenting the polypeptide on the surface of the cell, and immune effector cell thereof, a pharmaceutical composition containing the polypeptide, a vaccine containing the nucleic acid, the nucleic acid construct, the expression vector, the host cell, the antigen-presenting cell, and the immune effector cell, and an antibody recognizing the polypeptide. Also provided is a therapeutic method using the polypeptide, the nucleic acid, the pharmaceutical composition, the vaccine, and the antibody. Also provided are a diagnosis method and diagnosis apparatus for detecting the described polypeptide. Also provided is an application of the polypeptide in preparing a vaccine, a tumor diagnosis kit, or a pharmaceutical composition, and an application of the polypeptide or the nucleic acid as a test target in tumor diagnosis.

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.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

The present disclosure provides fusion proteins with improved signaling properties. Disclosed embodiments include fusion proteins that comprise an extracellular antigen-binding domain, a transmembrane domain, and an intracellular component comprising one or more domain or motif from a CD3?, ?, or ? protein, and have improved signaling in response to antigen-binding, including of antigens with reduced, low, or intermediate levels of expression on a target cell, such as a solid tumor cell. Recombinant host cells expressing the fusion proteins are also provided, as well as compositions and methods comprising the same.