Bi-specific CAR-T cells are disclosed for treating NSCLCs. The disclosed CAR-T cells contain CAR polypeptides that can bind EGFR/MUC1-expressing cells. Therefore, also disclosed is an immune effector cell genetically modified to express an anti-EGFR CAR binding agent and an anti-MUC1 binding agent. Also disclosed are methods of providing an anti-tumor immunity in a subject with a EGFR and MVUC1-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

The present invention provides a cell-based platform for controllable, regionalized, and cost-effective delivery of immunomodulator and other therapeutic proteins, which is widely applicable in cancer immunotherapy.

The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

The present invention is directed to a chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) having activity against tumor antigen, (ii) a transmembrane domain, (iii) at least one co-stimulatory domain having one or more binding motifs immediately repeated at least one time, and (iv) an activating domain. A preferred co-stimulatory domain is derived from human CD28, 4-1BB, ICOS-1, CD27, OX-40, GITR, or DAP10.

Provided is a method of activating a recombinant immune cell expressing a synthetic receptor comprising an intracellular domain derived from killer cell immunoglobulin-like receptor 4 (KIR2DL4). Synthetic receptors described herein allow for the activation of recombinant immune cells against an antigen of interest without the deleterious effects of immune cell hyperactivation by existing CARs. The recombinant immune cells can thus be used to in the treatment of cancers or infectious diseases in subjects in need thereof, while limiting the hyperactivation of an immune response associated with traditional recombinant cell-based therapies.

The present invention provides compositions and methods comprising CAR T cells that secrete neuraminidase (e.g., C. perfringens neuraminidase (CpNA)). Compositions and methods of treatment are also provided.

Disclosed herein are polynucleotides encoding ligand-inducible gene switch polypeptides, and systems comprising gene switch polypeptides for modulating the expression of a heterologous gene and an interleukin in a host cell. The compositions, methods and systems described herein facilitate ligand dependent expression of polypeptides including but not limited to cytokines and antigen binding polypeptides.

The present disclosure provides improved chimeric co-stimulatory receptors (CCRs), fusion proteins, genetically modified immune effector cells, and use of these compositions to treat disease.

The present specification provides not only an antigen-specific T cell receptor but also a nucleic acid, a vector, and an immune cell comprising the T cell receptor, and a method using same.

The present disclosure relates to EGFR-derived polypeptides containing short juxtamembrane sequences, nucleic acids encoding them, and methods of using them to improve cell surface expression of truncated EGFR markers.