The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors. The signals of the activating and blocking receptors can be modulated via the identity of a hinge.

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, and the levels of expression of the receptors are based on antigen levels on cells from a sample.

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, that exhibit cross-talk between the receptors.

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, and exhibit multiplex and localized activity.

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, which form into micro-clusters upon contacting a target or non-target cell.

The present disclosure provides engineered immune cells with activating and blocking receptors. The distance between the receptors is controlled to modulate the receptor signal strength.

The present disclosure is broadly concerned with the field of cancer immunotherapy. For example, the present invention generally relates to an immune cell comprising a genetically engineered antigen receptor that specifically binds to a target antigen and a genetic disruption agent that reduces or is capable of reducing the expression in the immune cell of a gene that weakens the function of the immune cell.

This disclosure provides for chimeric receptor polypeptides where upon binding of a first antigen to the antigen binding domain triggers a proteolytic cleavage and upregulation of a chimeric antigen receptor, wherein the chimeric antigen receptor binds to a second antigen. The first and second antigens are present on a population of B cells known as Autoimmune- or Age-related B cells or CD11c+T-bet+ B cells. The present disclosure includes methods and compositions for reducing or eliminating ABCs through the binding of the chimeric antigen receptor, and thus controlling or eliminating autoimmune disease.

Methods to create chemically-induced dimerizing (CID) protein systems and uses thereof are described. The methods utilize antibody binding domain dimerizing proteins. The created systems can be used to regulate cellular events such as gene expression, receptor signaling and cell death to effectuate a variety of clinically relevant treatment outcomes.

Novel chimeric proteins may be used to inhibit transcriptional activities that are mediated by transcription factor interactions with P-TEFb. The chimeras contain elements that recruit the target transcription factor, maintain CDK9 in an inactive state, and competitively inhibit P-TEFb binding to the transcription factor. The chimeras may be configured for inhibition of HIV Tat mediated transcription and thus provide a novel means of preventing reactivation of integrated HIV, providing a new tool for emerging “block and lock” HIV cure strategies.