Embodiments described herein relate to compositions including genetically modified CAR cells and uses thereof for treating cancer. Some embodiments of the present disclosure relate to compositions and methods for T cell response enhancement and/or CAR cell preparation. For example, a method may include obtaining cells comprising a CAR and culturing the cells in the presence of an agent that is recognized by the extracellular domain of the CAR.

Provided herein are acute myeloid leukemia antigen targets for chimeric receptors and methods of using same.

The present invention relates to methods for targeted insertion of at least one nucleic acid sequence/s of interest into a target genomic locus of a mammalian cell. More specifically, the methods of the invention are based on using nucleic acid cassettes comprising the nucleic acid sequence/s of interest and at least one recognition signal sequence (RSS), for insertion of the nucleic acid sequence of interest into the target genomic locus that is mediated by RAG-catalyzed recombination. The invention further provides cassettes, vectors and vehicles and cells comprising said cassettes, compositions and uses thereof in immunotherapy.

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.

Embodiments of the disclosure encompass methods and compositions that enhance adoptive cell therapy by preventing or at least reducing on-target off-tumor effects of adoptive cell therapy. The disclosure concerns an immune effector cells of any type that are engineered to express two separate chimeric molecules: an activating chimeric antigen receptor that activates the immune effector cell through costimulatory domains following binding to a first antigen, and an inhibitory chimeric antigen receptor that inhibits cell-mediated activation upon binding to a second antigen. In specific cases, the inhibitory chimeric antigen receptor prevents fratricide and exhaustion by inhibiting activation of the cell through the activating chimeric antigen receptor when the inhibitory chimeric antigen receptor binds a particular antigen, including one adopted by sibling engineered immune effector cells through trogocytosis.

This document relates to methods and materials for treating a mammal having an autoimmune disease. For example, materials and methods for producing an immuno-activatable cell comprising a first chimeric antigen receptor and a second chimeric antigen receptor are provided. Methods and materials for treating a mammal having an autoimmune disease comprising administering an immuno-activatable cell are also provided.

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.

The present invention provides a cell which comprises a first chimeric antigen receptor (CAR) and a second CAR, wherein the first and second CARs bind different epitopes on the same ligand. The cell may be used in a method for treating a disease, such as cancer.

Embodiments described herein relate to compositions including genetically modified CAR cells and uses thereof for treating cancer. Some embodiments of the present disclosure relate to compositions and methods for T cell response enhancement and/or CAR cell preparation. For example, a method may include obtaining cells comprising a CAR and culturing the cells in the presence of an agent that is recognized by the extracellular domain of the CAR.

The present invention relates to a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the first CAR is an activating CAR comprising an activating endodomain and the second CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain; wherein the first CAR binds to a first antigen and the second CAR binds to a second antigen, wherein both the first and second antigens are expressed on the surface of a target cell; wherein the first CAR binds to an epitope on the first antigen which is relatively proximal to the membrane of the target cell, the second CAR binds to an epitope on the second antigen which is relatively distal to the membrane of the target cell, in comparison with the epitope of the first antigen; and wherein the spacer of the first CAR is an equivalent size to the spacer of the second CAR.