Abstract: The present application relates to the field of immunotherapy, more particularly to the manufacture of cells for adoptive cell therapy. Provided herein are compositions and methods for improving in vivo persistence of cells intended for adoptive transfer. This is achieved by making the cells less vulnerable to clearance caused by NK cells of the subject receiving the adoptive cell therapy.

Abstract: The present application relates to the field of immunotherapy, more particularly to the field of chimeric antigen receptors (CARs). Currently, second and third generation CAR designs are quite rigid in that they combine fixed costimulatory domains in cis on the same intracellular protein domain. Trans signaling is not equivalent as costimulatory receptors have different expression levels or stoichiometry. Here, a ‘mix and match’ approach is proposed where different signaling and costimulatory domains are present on separate chains within the same CAR complex, allowing increased flexibility and control of the nature and strength of the CAR-generated signal. Also proposed are polynucleotides, vectors encoding the transmembrane polypeptide chains and cells expressing such CARs. These cells are particularly suitable for use in immunotherapy, and strategies to treat diseases such as cancer using these cells are also provided.

Abstract: The present application relates to the field of immunotherapy, more particularly to the field of chimeric antigen receptors (CARs). Currently, second and third generation CAR designs are quite rigid in that they combine fixed costimulatory domains in cis on the same intracellular protein domain. Trans signaling is not equivalent as costimulatory receptors have different expression levels or stoichiometry. Here, a ‘mix and match’ approach is proposed where different signaling and costimulatory domains are present on separate chains within the same CAR complex, allowing increased flexibility and control of the nature and strength of the CAR-generated signal. Also proposed are polynucleotides, vectors encoding the transmembrane polypeptide chains and cells expressing such CARs. These cells are particularly suitable for use in immunotherapy, and strategies to treat diseases such as cancer using these cells are also provided.

Abstract: The present application relates to the field of immunotherapy, more particularly to the manufacture of cells for adoptive cell therapy. Provided herein are compositions and methods for improving in vivo persistence of cells intended for adoptive transfer. This is achieved by making the cells less vulnerable to clearance caused by NK cells of the subject receiving the adoptive cell therapy.

Abstract: The present application relates to the field of immunotherapy, more particularly to the manufacture of cells for adoptive cell therapy. Provided herein are methods to prevent and/or reduce fratricide during manufacturing of such cells, particularly of cells expressing a chimeric NKG2D receptor. Also provided are cells and compositions comprising cells in which fratricide is prevented and/or reduced.

Abstract: The present application relates to the field of immunotherapy, more particularly to the manufacture of cells for adoptive cell therapy. Provided herein are methods to prevent and/or reduce fratricide during manufacturing of such cells, particularly of cells expressing a chimeric NKG2D receptor. Also provided are cells and compositions comprising cells in which fratricide is prevented and/or reduced.

Abstract: The present application relates to the field of immunotherapy, more particularly to the manufacture of cells for adoptive cell therapy. Provided herein are compositions and methods for improving in vivo persistence of cells intended for adoptive transfer. This is achieved by making the cells less vulnerable to clearance caused by NK cells of the subject receiving the adoptive cell therapy.

Abstract: The present application relates to the field of immunotherapy, more particularly to the field of chimeric antigen receptors (CARs). Currently, second and third generation CAR designs are quite rigid in that they combine fixed costimulatory domains in cis on the same intracellular protein domain. Trans signaling is not equivalent as costimulatory receptors have different expression levels or stoichiometry. Here, a ‘mix and match’ approach is proposed where different signaling and costimulatory domains are present on separate chains within the same CAR complex, allowing increased flexibility and control of the nature and strength of the CAR-generated signal. Also proposed are polynucleotides, vectors encoding the transmembrane polypeptide chains and cells expressing such CARs. These cells are particularly suitable for use in immunotherapy, and strategies to treat diseases such as cancer using these cells are also provided.

Abstract: The present application relates to the field of immunotherapy, more particularly to the manufacture of cells for adoptive cell therapy. Provided herein are methods to prevent and/or reduce fratricide during manufacturing of such cells, particularly of cells expressing a chimeric NKG2D receptor. Also provided are cells and compositions comprising cells in which fratricide is prevented and/or reduced.