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: A method for designing a chimeric antigen receptor (CAR), comprising: a) defining a training set of CAR sequences wherein each training CAR is associated with one or more properties; b) defining one or more objectives, each of the one or more objectives defining a desired property of a CAR; c) training a computational model using the training set of the one or more training CAR sequences to provide a trained computational model; d) using the computational model to provide at least one output CAR sequence, and wherein the at least one output CAR sequence is determined based on the one or more objectives. Methods of training a computational model for designing a chimeric antigen receptor (CAR), the trained model provided by such method, along with a CAR sequence output, the CAR encoded by the output CAR sequence and a cell expressing said CAR 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: A method for high-throughput screening of a chimeric antigen receptor (CAR) cell library is provided comprising the steps of (a) providing a recognition sequence library, a hinge region sequence library, a transmembrane sequence library and an intracellular domain sequence library; (b) preparing a CAR library; (c) preparing a CAR-cell library by introduction to, and expression of, the plurality of CAR sequences of the CAR library in one or more cells or a cell line; (d) screening the CAR-cell library in an assay; (e) evaluating the at least one function of each member of the CAR-cell library; (f) obtaining one or more sequences of one or more CARs expressed in the CAR-cell library and linking the obtained sequence(s) to the at least one function of the members of the CAR-cell library; g) identifying and selecting the or each sequence based on function. Methods of preparing the CAR library and a CAR-cell library and uses thereof 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.

Abstract: The present invention relates to chimeric receptors (e.g. CARs including both single chain and multichain CARs) that bind to TREM2 ligands and their use in therapy. In particular, the invention provides a chimeric receptor comprising: (a) an exodomain comprising the ligand binding domain of TREM2 or a functional variant thereof, optionally wherein said exodomain is resistant to cleavage by a sheddase; (b) a transmembrane domain; and (c) an endodomain comprising an intracellular signalling domain.

Abstract: The present invention relates to a polypeptide comprising a sequence having the formula R1-L-R2-St wherein R1 and R2 are Rituximab-binding epitopes; St is a stalk sequence which, when the polypeptide is expressed at the surface of a target cell, causes the R1 and R2 epitopes to be projected from the cell surface; and L is a flexible linker sequence which connects the C terminus of R1 to the N terminus of R2. In particular, the linker sequence does not comprise a QBEnd10 binding epitope comprising the sequence set out in SEQ ID NO.1. The polypeptide functions as a suicide moiety which enables cells expressing the polypeptide to be deleted, and is useful in adoptive cell therapy. Also provided is a nucleic acid encoding such a polypeptide, a cell comprising such a nucleic acid and therapeutic uses thereof.

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 field of adoptive cell therapy (ACT). Here, shRNAs designed to downregulate CD52 are proposed. Also proposed are polynucleotides, vectors encoding the shRNA and cells expressing such shRNAs, alone or in combination with a chimeric antigen receptor (CAR). These cells are particularly suitable for use in immunotherapy, especially in combination with immunosuppressive therapies directed against CD52, as is particularly envisaged in allogeneic therapy. The invention provides methods of increasing the efficacy of a T cell therapy in a patient in need thereof. Further, strategies to treat diseases such as cancer using these cells are also provided. The engineered immune cells, such as T-cells or natural killer (NK) cells, expressing such CARs are particularly suitable for treating lymphomas, multiple myeloma and leukemia.

Abstract: The present application relates to the field of immunotherapy, more particularly to the field of chimeric antigen receptors (CARs). Here, CARs are proposed that are directed against B-cell Maturation Antigen (BCMA, also known as CD269). 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. The engineered immune cells, such as T-cells or natural killer (NK) cells, expressing such CARs are particularly suitable for treating lymphomas, multiple myeloma and leukemia.

Abstract: The present application relates to the field of immunotherapy, more particularly to the field of adoptive cell therapy (ACT). Here, multiple shRNAs, designed to downregulate multiple targets are proposed. Also proposed are polynucleotides, vectors encoding the shRNA and cells expressing such shRNAs, alone or in combination with a chimeric antigen receptor (CAR). These cells are particularly suitable for use in immunotherapy.

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.