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: This document relates to catheter-based therapeutic apparatus and methods for directing therapy within the body of a subject. This document also encompasses a control handle comprising a steering assembly and a delivery assembly suitable for use in conjunction with the catheter-based therapeutic apparatus to provide steering and fine positional control of the catheter tip.

Abstract: The invention relates to an injection catheter for delivering a therapeutic agent into a substrate, comprising one or more lumens and a curved delivery element, said lumen serving as a guide for said curved delivery element outside of the substrate; said curved delivery element comprising openings on its distal tip, said distal tip comprising a distal zone and a proximal zone, said injection catheter being characterized in that the specific surface in said distal zone of said distal tip of said curved delivery element is higher than the specific surface in said proximal zone of said distal tip of said curved delivery element. The invention also relates to a process for delivering a therapeutic agent into a substrate.

Abstract: The present invention is related to a pharmaceutical composition comprising cells committed to the generation of heart tissue and at least one pharmaceutically acceptable excipient produced according to internationally recognized standards for pharmaceutical product manufacture, a process for the manufacture of such a pharmaceutical composition and a kit for the administration of said pharmaceutical composition which comprises a container containing said pharmaceutical composition.

Abstract: The present invention is related to a pharmaceutical composition comprising cells committed to the generation of heart tissue and at least one pharmaceutically acceptable excipient produced according to internationally recognized standards for pharmaceutical product manufacture, a process for the manufacture of such a pharmaceutical composition and a kit for the administration of said pharmaceutical composition which comprises a container containing said pharmaceutical composition.