The present invention provides a genetically modified NK cell line prepared by transducing host NK cell line with a gene construction encoding a cancer antigen-specific chimeric antigen receptor (CAR) comprising a FLT3-specific monoclonal antibody or a functional fragment thereof, a transmembrane domain, and a CD3ζ domain of a T-cell receptor for more efficient immunotherapy of acute myeloid leukemia, and use thereof, for more efficient immunotherapy of acute myeloid leukemia.

The present invention relates to a recombinant virus of the family Paramyxoviridae comprising an expressible polynucleotide encoding at least one of (i) a tumor antigen, (ii) a fragment of a tumor antigen, and (iii) a variant of (i) or (ii). The present invention further relates to a polynucleotide encoding said recombinant virus of the family Paramyxoviridae and to a host cell comprising said recombinant virus of the family Paramyxoviridae and/or said polynucleotide encoding said recombinant virus of the family Paramyxoviridae. Moreover, the present invention relates to a method for activating immune cells with antitumor activity in a sample comprising cancer cells and to further means, methods, and uses related to the present invention.

The present invention in general to intranasal mRNA vaccines, more in particular comprising one or more immunostimulatory molecules, one or more pathogenic antigens and a specifically designed delivery system. Specifically said immunostimulatory molecules and pathogenic antigens are provided for in the form of mRNA molecules encoding such molecules and antigen; more in particular mRNA molecules encoding for CD40L, caTLR4 and/or CD70 in combination with one or more mRNA molecules encoding a bacterial, viral or fungal antigen. Specifically said, the delivery is a mixture of chemical compounds that allow protection and deposition of the vaccine and targeting to the antigen presenting cells in the nose. In particular, present invention is well suited for development of a rapid response vaccine in an outbreak setting.

The invention is directed to a process for providing a cell comprising a chimeric antigen receptor (CAR) specific for one or more target antigens exposed on tumor microenvironment cells characterized by providing a cell sample comprising tumor microenvironment cells and non-tumor microenvironment cells and repeating the steps of—contacting the cell tissue with a conjugate comprising a fluorescent moiety and an antigen recognizing moiety—removing unbound conjugate from the cell tissue and detecting cells bound to the conjugate by the fluorescence radiation emitted by the fluorescent moieties of the first conjugates—erasing the fluorescence emitted by the fluorescent moieties of the conjugates until identifying at least two conjugates provided with antigen recognizing moieties recognizing different antigens, allowing in combination to discriminate between tumor microenvironment cells and non-tumor microenvironment cells and providing cells with the identified at least two antigen recognizing moieties as chimeric antigen receptor (CAR). Preferable, the tumor microenvironment cells are tumor microenvironment cells from tumor stromal cells or PaCa cells.

D domain (DD) containing polypeptides (DDpp) that specifically bind targets of interest (e.g., BCMA, CD123, CS1, HER2, AFP, and AFP p26) are provided, as are nucleic acids encoding the DDpp, vectors containing the nucleic acids and host cells containing the nucleic acids and vectors. DDpp such as DDpp fusion proteins, are also provided as are methods of making and using the DDpp. Such uses include, but are not limited to diagnostic and therapeutic applications.

Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of CD33-binding antibodies are described. The CARs include optimized short and intermediate spacer regions. The current disclosure also provides methods of cell expansion/activation processes utilizing IL-2, IL-7, IL-15, and/or IL-21 that improve cellular proliferation and cell lysis of the CARs as described.

Control Devices are disclosed including RNA destabilizing elements (RDE) combined with transgenes, including Chimeric Antigen Receptors (CARs) in eukaryotic cells. These RDEs can be used to optimize expression of transgenes, e.g., CARs, in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered at desired times from the eukaryotic cell. Such CAR T-cells with transgene payloads can be combined with the administration of other molecules, e.g., other therapeutics such as anticancer therapies.

The present disclosure provides systems for inducing activity of immune cells and methods of immunotherapy. Systems of the present disclosure for inducing immune cell activity comprise a chimeric antigen receptor, a T cell receptor, and various combinations thereof.

The invention provides compositions and methods improved CAR T cell therapies. Specifically, the invention provides cells with reduced Tet, e.g., Tet2 function or expression, and methods of use therefore. The invention further provides Tet2 inhibitors and methods of use therefore in connection with CAR T cells.

The present invention relates to bispecific antibodies which bind to human carcinoembryonic antigen CEACAM5 (CEA) and human CD3ε. In addition, the present invention relates to polynucleotides encoding such bispecific antibodies and vectors and host cells comprising such polynucleotides. The invention further relates to methods for selecting and producing such antibodies and to methods of using such antibodies in the treatment of diseases.