Recombinant proteins that stimulate an immune response in the presence of naturally inhibitory ligand binding are described. The recombinant proteins include an extracellular domain of an inhibitory immune cell protein and an intracellular domain of a stimulatory immune cell protein connected via a transmembrane domain. The recombinant proteins can be used to stimulate immune cell activation in the fight against cancers and infectious diseases, among other uses.

The present invention is in the field of cell-based immunotherapies. In particular, the invention provides a modified cell comprising a first and second polypeptide forming an antigen-binding site at the external side of the cell, and a polypeptide comprising a signaling domain, wherein, upon binding of the antigen-binding site to a corresponding antigen, the signaling domain triggers a process in the cell that enables the cell to promote death of a target cell comprising said antigen on the cell surface. The invention also provides medical uses of the modified cell, in particular for use in the treatment of diseases. Furthermore, the invention provides a kit comprising at least one nucleic acid molecule encoding said polypeptides, and methods for producing the modified cells of the invention. In addition, the invention provides chimeric polypeptides and nucleic acid molecules encoding chimeric polypeptides.

The present invention is in the field of cell-based immunotherapies. In particular, the invention provides a modified cell comprising a first and second polypeptide forming an antigen-binding site at the external side of the cell, and a polypeptide comprising a signaling domain, wherein, upon binding of the antigen-binding site to a corresponding antigen, the signaling domain triggers a process in the cell that enables the cell to promote death of a target cell comprising said antigen on the cell surface. The invention also provides medical uses of the modified cell, in particular for use in the treatment of diseases. Furthermore, the invention provides a kit comprising at least one nucleic acid molecule encoding said polypeptides, and methods for producing the modified cells of the invention. In addition, the invention provides chimeric polypeptides and nucleic acid molecules encoding chimeric polypeptides.

This disclosure provides compositions and methods for improving immunotherapy, specifically against diseases like HIV or lymphoma that manifest within B cell follicles.

This disclosure provides compositions and methods for improving immunotherapy, specifically against diseases like HIV or lymphoma that manifest within B cell follicles.

The invention pertains to the field of adaptive cell immunotherapy. It provides with the genetic insertion of exogenous coding sequence(s) that help the immune cells to direct their immune response against infected or malignant cells. These exogenous coding sequences are more particularly inserted under the transcriptional control of endogenous gene promoters that are sensitive to immune cells activation. Such method allows the production of safer immune primary cells of higher therapeutic potential.

The invention pertains to the field of adaptive cell immunotherapy. It provides with the genetic insertion of exogenous coding sequence(s) that help the immune cells to direct their immune response against infected or malignant cells. These exogenous coding sequences are more particularly inserted under the transcriptional control of endogenous gene promoters that are sensitive to immune cells activation. Such method allows the production of safer immune primary cells of higher therapeutic potential.

The present invention relates generally to a fusion protein that when displayed on a cell can convert a negative signal into a positive signal in the cell. The fusion protein is a chimeric protein in that the protein comprises at least two domains, wherein the first domain is a polypeptide that is associated with a negative signal and the second domain is a polypeptide that is associated with a positive signal. Thus, the invention encompasses switch receptors that are able to switch negative signals to positive signals for enhancement of an immune response.

A chimeric polypeptide, containing a binding peptide that can specifically bind to a target molecule, a receptor regulatory domain containing one or more cleavage sites, and an intracellular domain. The receptor regulatory domain comprises an extracellular region and a transmembrane region, wherein the extracellular region and the transmembrane region are not both derived from a Notch protein. The binding of the binding peptide to the target molecule can induce the cleavage of the receptor regulatory domain, thereby releasing the intracellular domain.

Disclosed herein are an engineered immune cell with CIITA gene knock-out and use thereof. According to the present invention, an sgRNA specifically targeting CIITA gene is designed and synthesized, which can accurately target CIITA gene to achieve gene knock-out with high knockout efficiency. The provided sgRNA can be used for preparing a universal CAR-T cell.