Described herein are chimeric receptors. Chimeric receptors comprise a cytoplasmic domain; a transmembrane domain; and an extracellular domain. In embodiments, the cytoplasmic domain comprises a cytoplasmic portion of a receptor that when activated polarizes a macrophage. In further embodiments, a wild-type protein comprising the cytoplasmic portion does not comprise the extracellular domain of the chimeric receptor. In embodiments, the binding of a ligand to the extracellular domain of the chimeric receptor activates the intracellular portion of the chimeric receptor. Activation of the intracellular portion of the chimeric receptor may polarize the macrophage into an M1 or M2 macrophage.

Methods of treating a cancer in a patient are provided. The methods can include obtaining a tumor sample from a patient, detecting whether CCNG1 gene expression is present in the tumor sample, diagnosing the patient with a CCNG1 inhibitor-responsive cancer when the presence of CCNG1 gene expression in the tumor sample is detected, and/or administering an effective amount of a CCNG1 inhibitor to the diagnosed patient. CCNG1 inhibitors can include a viral vector having a binding peptide that is configured to bind one or more signature (SIG) elements of an invading tumor and at least one cytocidal gene. CCNG1 inhibitors including cell penetrating peptides are also provided.

The disclosure relates to synthetic super-enhancers activated by one or more transcription factors. In particular, the present disclosure describes synthetic super-enhancers that are activated by one or more transcription factors expressed in a target cell and used to express transgenes, such as adverse payloads, upon activation of the synthetic super-enhancer by the transcription factor(s).

The present invention relates to an oncolytic virus and the use thereof, specifically, an oncolytic virus having suppressed thymidine kinase (TK) gene expression and comprising genes encoding granulocyte-macrophage colony-stimulating factor (GM-CSF) and a complement regulatory protein; and the use of such an oncolytic virus. The oncolytic virus of the present invention maintains its efficacy even when administered intravenously, and thus, it may also be applied to the treatment of various solid cancers and metastatic cancers in addition to superficial solid cancers. In addition, the oncolytic virus of the present invention acquires resistance to complement attack by expressing a complement regulatory protein on the surface of the virus, and thus, it is stable in the blood, and it maintains stable oncolytic activity when intravenous injection, and thus, it may reduce effective viral dosage to minimize the side effects of anti-cancer drugs.

Provided herein are genetically engineered mammalian (e.g., human) cells that express one or more transgenes at a sustained expression level. Also provided are methods of making and using the cells.

In one aspect, the present disclosure relates to tumor associated macrophage (TAM) targeting peptide. In another aspect, the present disclosure relates to a method of targeting a TAM in a subject, the method comprising administering to the subject a TAM targeting peptide attached to and/or displayed on the surface of a solid particle. In yet another aspect, the present disclosure relates to a method of treating a tumor infiltrated with a TAM in a subject, the method comprising administering to the subject a TAM targeting peptide attached to and/or displayed on the surface of a solid particle.

The invention provides pluripotent cells that are used therapeutically for regenerating tissues but avoid rejection by subjects that receive them. In particular, the invention provides hypo-immunogenic pluripotent cells that avoid host immune rejection. The cells lack major immune antigens that trigger immune responses and are engineered to avoid phagocytic endocytosis. The invention further provides universally acceptable off-the-shelf pluripotent cells and derivatives thereof for generating or regenerating specific tissues and organs.

Disclosed are compositions and methods for treating a disease or disorder such as cancer in a subject in need thereof. In some aspects, the method comprises administering to the subject a vector comprising a first nucleic acid sequence encoding a promoter operably linked to each of a second nucleic acid sequence encoding a therapeutic polypeptide, and a third nucleic acid sequence encoding a peptide domain that is stabilized when phosphorylated by kinase activity in a target tissue. The kinase activity can be elevated extracellular regulated kinase (ERK) activity.

Nucleic acid sequences encoding improved Herpes Simplex Virus Thymidine Kinases are provided, including their use in diagnostic and therapeutic applications. The thymidine kinases may be mutated using conservative mutations, non-conservative mutations, or both. Also provided are gene therapeutic systems, including viral and retroviral particles.

Described herein are chimeric receptors. Chimeric receptors comprise a cytoplasmic domain; a transmembrane domain; and an extracellular domain. In embodiments, the cytoplasmic domain comprises a cytoplasmic portion of a receptor that when activated polarizes a macrophage. In further embodiments, a wild-type protein comprising the cytoplasmic portion does not comprise the extracellular domain of the chimeric receptor. In embodiments, the binding of a ligand to the extracellular domain of the chimeric receptor activates the intracellular portion of the chimeric receptor. Activation of the intracellular portion of the chimeric receptor may polarize the macrophage into an M1 or M2 macrophage.