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.

Provided herein are, inter alia, methods and compositions including T cells expressing (i) a recombinant CAR protein which includes a peptide binding site and is capable of specifically binding cancer-specific antigens and (ii) a T cell receptor specific for a viral antigen (e.g., a CMV pp65 protein). The engineered T cells provided herein may be used in combination with a viral vaccine (e.g. cytomegalovirus (CMV) Triplex Vaccine) to treat a variety of cancers. The methods described herein also permit in vivo expansion of CMV-specific CAR T cells, instead of or in addition to ex vivo expansion, avoiding excessive T cell exhaustion that results in some cases from ex vivo manufacturing.

The present invention provides a chimeric antigen receptor (CAR) fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) comprising V.sub.H and V.sub.L, wherein scFv has an activity against CD47, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. In one embodiment, the scFv is derived from a humanized anti-CD47 antibody. The present invention also provides T cells modified to express the CAR of the present invention.

The present invention relates to new CD22 Chimeric Antigen Receptors (CD22 CAR), an engineered immune cell endowed with said new CD22 CAR and comprising at least inactivated TRAC gene for use in therapy. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.

Embodiments of the present disclosure include a method for treating Systemic Lupus Erythematosus (SLE) using CD19 CAR T cells. The method includes administering to the human patient a pharmaceutically effective amount of a population of T cells of the human patient that express a chimeric antigen receptor (CAR) that comprises the amino acid sequence of, e.g., SEQ ID NO: 23.

Some embodiments provided herein are chimeric costimulatory antigen receptor (CoStAR), useful in adoptive cell therapy (ACT), and cells comprising the CoStAR. In some embodiments, the CoStAR can act as a modulator of cellular activity enhancing responses to defined antigens. In some embodiments, CoStAR and/or fusion proteins, nucleic acids encoding the CoStAR and therapeutic uses thereof are also provided.

The present invention provides for a hybrid sugar transporter having an altered sugar transporter activity and comprising at least a first transmembrane domain (TMD) from a first sugar transporter and a second TMD from a second sugar transporter, wherein the first sugar transporter and the second sugar transporter are heterologous to each other.

Several embodiments disclosed herein relate to the compositions comprising engineered Natural Killer (NK) cells that express a chimeric receptor, the chimeric receptor imparting to the NK cells an enhanced ability to target specific cells, such as cancerous cells or those affected by an infectious disease. Several embodiments relate to NK cells that target cells expressing natural ligands of NKG2D, where the NK cells comprise transmembrane and/or signaling domains that lead to cytotoxic and/or cytolytic effects when the NK cells bind a target cell. Uses of NK cell compositions to treat diseases are also provided for in several embodiments.

Sortase molecules and methods described herein allow for the construction of a CAR or CAR member, e.g., in situ, on a CARX, e.g., CART, cell. For example, sortase mediated transfer of an antigen binding domain, e.g., a scFv, onto a CAR member having a sortase acceptor motif in place of an antigen binding domain can provide for a complete CAR member on a cell wherein the cell does not comprise nucleic acid that encodes the complete CAR member.

The invention provides chimeric antigen receptors (CARs) that specifically bind to the T-cell immunoglobulin and mucin domain 1 (TIM-1) protein. The invention further relates to modified immune cells, e.g., T or NK cells, comprising such CARs, CAR-encoding nucleic acids, CAR-encoding vectors, and methods of making such compositions. The invention further relates to methods for therapeutic use of these CARs and modified immune cells for the treatment of a condition, disorder, or disease associated with cells expressing TIM-1 (e.g., cancer).