The present disclosure provides a chimeric antigen receptor including a target antigen-binding domain, a transmembrane domain, and a signal transduction domain.

The present invention relates to engineered cells expressing a fusion protein comprising a peptide fusion inhibitor and a CXCR4 protein that lacks signaling activity. Also provided are methods of suppressing, inhibiting, preventing or treating a HIV infection in a subject in need thereof using the engineered cells.

Provided herein are compositions and methods for detecting migration of effector cells towards a target cell, and cytotoxicity of the migrated effector cells against the target cells. The effector cells are modified to express a homing or migratory receptor, and the target cells are modified to express the cognate ligand. The methods can be carried out in a Boyden chamber or tranwells with a porous membrane between the wells. The membrane can be coated with an extracellular matrix component to simulate a solid tumor environment.

The risk with introducing manipulated T-cell is unforeseen adverse events. During the development of chimeric antigen receptor (CAR) T-cell therapies almost all clinical trial has shown some adverse events ranging from cytokine mediated toxicities to tissue damage and death. By the present invention, we aim to induce multiple layers of safety checkpoints. As a last resort we will be able to induce suicide in all cells which we have introduced to the body. Here we describe the scientific background to the parts of our suicide switch and the details regarding the proteins which are included. Safety switches are being tested on CAR-T cells, but they have a few drawbacks. Due to the limited space on the CAR vector, there is only room for one gene switch. Presently the results show they induce apoptosis in around 70-90% of cells, while the desired target is for all cells to be removed from the tissue. By utilising the space available on a synthetic chromosome, we can include multiple genes under Tet operons which allow us to turn multiple genes on/off. Life or death of a cell depends on the balance of the pro and anti-apoptotic proteins. The scale is always shifting a bit back and forth but only when tipped completely over the apoptotic cascade is initiated. By fine tuning the balance we aim to ensure that the hSync carrying cells have a survival advantage in the tumour in the absence of inducing agent. On the other hand, the moment that agent is administrated the cells will undergo apoptosis and express find me and eat me markers making sure they are removed without risk of tissue damage. The present invention encompasses compositions and methods for use in cellular gene therapeutics using a modular approach to genetically engineer cells to carry a synthetic chromosome having a regulatable system including one or more safety switches.

The present disclosure provides a cell comprising: an anti-CD33 chimeric antigen receptor (CAR); an anti-CLL 1 CAR; and an anti-CD123 and/or anti-CAR FLT3 CAR. The cell can be used in the treatment of a disease such as acute myeloid leukemia (AML).

Provided herein are compositions and methods for detecting migration of effector cells towards a target cell, and cytotoxicity of the migrated effector cells against the target cells. The effector cells are modified to express a homing or migratory receptor, and the target cells are modified to express the cognate ligand. The methods can be carried out in a Boyden chamber or tranwells with a porous membrane between the wells. The membrane can be coated with an extracellular matrix component to simulate a solid tumor environment.

Provided herein are modified NK-92 cells comprising a nucleic acid encoding C-C chemokine receptor type 7 (CCR7) operably linked to a promoter. Optionally, the cells further comprise a nucleic acid encoding C-C motif ligand 21 (CCL21), a nucleic acid encoding C-C motif ligand 19 (CCL19) or a combination thereof. Also provided are compositions and kits comprising the modified NK-92 cells. Provided are methods of making the modified cells and methods of treating cancer using the cells.

Provided herein are modified NK-92 cells comprising one or more nucleic acids encoding i) a homing receptor, ii) Antigen Binding Protein (ABP) or Chimeric Antigen Recpetor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Further provided herein are modified NK-92 cells comprising one or more nucleic acids encoding i) IL-12 and/or TGF-beta trap, ii) an Antigen Binding Protein (ABP) or Chimeric Antigen Recpetor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Also provided are compositions and kits comprising the modified NK-92 cells, as well as methods of treating cancer using the modified cells.