Genetically engineered cd4 t-cells for in situ synthesis of proteins

A single construct configured to form a genetically engineered effector cell with an isolated CD4 T-cell for secretion of an effector protein upon recognition of an antigen on a surface of a target cell, the single construct comprising an exogenous polynucleotide sequence including, in operative association:

• a receptor element that encodes a chimeric antigen receptor (CAR) including an extracellular antigen binding domain operably linked to a transmembrane domain, and an intracellular signaling domain, wherein the extracellular antigen binding domain recognizes an antigen on a surface of a target cell;
• an actuator element that encodes a transcription factor binding site that upregulates synthesis of an effector protein in response to the extracellular antigen binding domain of the CAR binding to the antigen of the target cell;
• and
• an effector element that encodes the effector protein, wherein, in response to the extracellular antigen binding domain of the CAR binding to the antigen of the target cell, the genetically engineered effector cell is configured to activate and, to synthesize and secrete the effector protein.

A population of genetically engineered effector cells, each of the genetically engineered effector cells of the population comprising an isolated CD4 T-cell carrying an exogenous polynucleotide sequence that includes an actuator element bound to an effector element bound to a receptor element, wherein:

• a receptor element that encodes a chimeric antigen receptor (CAR) including an extracellular antigen binding domain operably linked to a transmembrane domain, and an intracellular signaling domain, wherein the extracellular antigen binding domain recognizes an antigen on a surface of a target cell;
• an actuator element that encodes a transcription factor binding site that upregulates synthesis of an effector protein in response to the extracellular antigen binding domain of the CAR binding to the antigen of the target cell;
• and
• an effector element that encodes the effector protein, wherein, in response to the extracellular antigen binding domain of the CAR binding to the antigen of the target cell, the population of genetically engineered effector cells is configured to activate and, to synthesize and secrete the effector protein.