In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

Embodiments of the disclosure include methods and compositions for enhancing expansion of immune cells for immunotherapy. In particular embodiments, immune cells, such as T-cells, express a constitutively active cytokine receptor in which the transmembrane and endodomains are able to provide an activating signal separately from any input to the corresponding exodomain to which they are operably linked. In specific embodiments, the transmembrane and endodomain from IL-7R is utilized with the exodomain of CD34.

Methods and compositions for treating cancer, particularly improved CAR-T methods, are disclosed.

The present application relates to a GD2-based chimeric antigen receptor comprising an antigen-binding domain, a transmembrane domain, a costimulatory signaling domain, a CD3 signaling domain, and a self-destructive domain in tandem arrangement; wherein the antigen-binding domain binds to a tumor surface antigen, wherein the tumor surface antigen is GD2, and the antigen-binding domain is a single-chain antibody against the tumor surface antigen GD2, wherein the self-destructive domain is a caspase 9 domain.

The present disclosure relates to CAR-T cells and uses thereof. Disclosed herein is a genetically modified T cell comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) polypeptide comprising a single-chain variable fragment (scFV) that specifically binds to a target molecule, wherein the nucleic acid sequence encoding the CAR polypeptide is integrated into an integration site located at a miR-155 host gene.

The present invention relates to an in vitro method for priming genetically modified T cells suitable for administration to a patient having a tumor. The invention is also directed to the composition obtained by the method and uses thereof.

Provision of a chimeric antigen receptor (CAR) comprising a disialoganglioside (GD2)-binding domain which comprises a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences: b) a light chain variable region (VL) having CDRs with the following sequences: T cells expressing such a CAR are useful in the treatment of some cancers.

Aspects of the disclosure relate to novel scFv molecules that are useful for incorporation into novel chimeric antigen receptors with enhance anti-tumor activity. Further aspects relate to a polypeptide comprising a CAR comprising, in order from amino proximal to carboxy proximal end, a scFv, a transmembrane domain, a torsional linker, and a cytoplasmic region comprising a primary intracellular signaling domain, wherein the torsional linker comprises 1-12 alanine residues. Also described are nucleic acids comprising a sequence encoding a polypeptide of the disclosure, vectors, such as lentiviral vectors comprising the nucleic acids of the disclosure, cells comprising and/or expressing nucleic acids and/or polypeptides of the disclosure, and populations of cells comprising the cell embodiments of the disclosure. Also provided are methods of making cells that express a polypeptide and methods of treating patients with the polypeptides and cell compositions of the disclosure.

The disclosure provides synthetic immune receptors (SIRs), nucleic acids encoding the SIRs, methods of making and using the SIRs, in, for example, adoptive cell therapy.

There is provided method for making a cell composition which comprises step of transducing a population of cells with a mixture of at least two viral vectors, wherein at least one vector comprises a nucleic acid sequence which encodes a chimeric antigen receptor (CAR); and wherein at least one vector comprises a nucleic acid encoding an activity modulator which modulates the activity of the CAR, of a cell expressing the CAR, or of a target cell. There is also provided a cell composition made by such a method and its use in the treatment of diseases such as cancer.