Provided are nucleic acids that encode decoy-resistant interleukin 18 (DR-18) polypeptides, as well as vectors and cells comprising such nucleic acids and cells that comprise such vectors. Cells encoding DR-18 polypeptides may be referred to as DR-18 armored cells. The nucleic acids may further encode a chimeric antigen receptor (CAR) or multiple CARs, including CARs that bind to antigens described herein. Methods are also provided, including methods of making the nucleic acids, vectors, and/or cells, as well as methods of use, such as employing the nucleic acids, vectors, and/or cells, in the treatment of a subject having cancer.

Provided herein are natural killer (NK) cells with increased, modified or deleted extracellular matrix (ECM) receptors, and methods of making and using the same for cancer immunotherapy, and treatment of chronic infections, inflammation, autoimmune diseases, or transplant rejection.

Described herein are engineered cytokine receptor switches that can include a signal peptide, an extracellular activator binding domain, a hinge, a transmembrane domain, and/or an intracellular signaling domain. Binding of an activator to the activator binding domain can activate cytokine signaling through the intracellular signaling domain. These cytokine receptor switches can be expressed in immune cells, sometimes in combination with a chimeric antigen receptor (CAR), to increase immune cell persistence by promoting adoption of memory-like phenotypes. Also described herein are methods of using engineered cytokine receptors in immune cell therapies, such as CAR T-cell therapy, to improve patient outcomes and prevent disease relapse.

The present invention relates to compositions and methods that provide novel therapies in cancer. The invention includes a phagocytic cell modified with a repressor of signal regulatory protein-alpha (SIRP) and bound to a targeting antibody to enhance phagocytic activity of the phagocytic cell toward tumor tissue. Methods of enhancing phagocytic activity and treating a tumor are also included.

Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of FcRI. Notably, CAR constructs with an intracellular domain of FcRI had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK/NK-92 cells.

Provided are tetravalent bispecific antibodies (T-BiAbs) that have a first binding moiety and a second binding moiety, wherein the first binding moiety is a single chain variable fragment (scFv) and the second, binding moiety-7 is a monoclonal antibody, and further wherein the variable light (Vi.) and variable heavy7 (VH) chains of the first binding moiety7 are directly linked as a. single chain to the second binding moiety at the N-terminus or the C-terminus of the light chain or the heavy chain sequence of the second binding moiety. In some embodiments, the first binding moiety binds to a CDS polypeptide and the second binding moiety-7 binds to a tumor-associated antigen. Also provided are T cells armed with the presently disclosed T-BiAbs and methods of using the same for treating tumor and/or cancers, treating diabetes, arming and isolating stem cells, and manufacturing medicaments for these purposes.

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, that exhibit cross-talk between the receptors.

Disclosed is a multimeric fusion protein and a method for producing the multimeric fusion protein. The method includes expressing in an mammalian cell a nucleic acid coding for an amino acid sequence comprising, in an N-terminal to C-terminal direction, a signal peptide, (optionally) an antigenic peptide, a CH3 domain of human IgG.sub.1, a (G-P-P).sub.10 collagen-like domain, and a TNF ligand superfamily extracellular domain, the extracellular domain being devoid of a coiled-coil trimerization motif, and allowing the polypeptides expressed in the mammalian cell from the nucleic acid to at least one of trimerize and hexamerize into one or more multimeric fusion proteins.

In certain embodiments, this disclosure provides methods to generate DNA, RNA and/or DNA-peptide nanostructures based chimeric antigen receptor (CAR) T cell (engineered T cell) for cancer immunotherapy, and compositions made by these methods.

The present disclosure provides a chimeric antigen receptor including a target antigen-binding domain, a transmembrane domain, and a signal transduction domain.