A method is disclosed for decreasing or retarding an increase in the size of a localized or metastatic tumor by using a combination of an immune stimulating cytotoxic gene therapy and immune-checkpoint modulating agent, in conjunction with other therapies, including radiation therapy, chemotherapy, surgery, and immunotherapies.

The disclosure relates to fusion proteins, methods of making fusion proteins, and methods of using fusion proteins, wherein the fusion proteins comprise a functional single-domain antibody (sdAb) or a functional variant thereof and a cytosine deaminase (CD) protein or a functional variant thereof, optionally connected via a peptide linker. The fusion proteins of the disclosure also have CD activity. The disclosure also relates to pharmaceutical compositions or formulations comprising such fusion proteins and pharmaceutically acceptable excipients, as well as medical uses of these fusion proteins.

This disclosure provides modified cytosine deaminases(CDs). The disclosure further relates to cells and vector expressing or comprising such modified CDs and methods of using such modified CDs in the treatment of disease and disorders.

A prodrug enzyme covalently photoconjugated to a live cell receptor survives endosomal proteolysis and retains its catalytic activity on the living cell membrane over multiple days. Antibody-directed enzyme prodrug therapy is a promising approach for selective treatment of solid tumors, but methods are needed to preserve enzyme activity on living cell membranes over multiple prodrug dosings. A fusion protein was designed with both an anti-epidermal growth factor receptor (EGFR) affibody and the prodrug enzyme cytosine deaminase, which can convert prodrug 5-fluorocytosine to the anticancer drug 5-fluorouracil. A benzophenone group was added at a site-specific mutation within the affibody portion, and the fusion protein was selectively and irreversibly photoconjugated to EGFR receptors expressed on membranes of live MDA-MB-468 breast cancer cells. Affinity-mediated covalent conjugation of the affibody-enzymes to cell receptors allows for prolonged expression on membranes and retained enzymatic activity without genetic engineering.

To treat brain dysfunctions, brain diseases or tumors, the present invention provides a cell preparation comprising neural stem cells differentiated from pluripotent stem cells into which a suicide gene has been introduced.

The present invention relates to: a recombinant lentiviral vector comprising a gene encoding a TRAIL protein and a CD protein; and a cell that is transfected with the lentivirus produced by using the vector. A host cell transfected with the recombinant lentivirus of the present invention maintains a high cell proliferation rate and overexpresses a TRAIL protein and a CD protein. Thus, a mesenchymal stem cell transfected with the lentivirus may be usefully employed as a cell therapeutic agent.

The disclosure provides an extended release formulation of 5-fluorocytosine. In another aspect, a method of treating a fungal disease is provided. The method comprises administering to a subject in need thereof a fungus-treating effective amount of a composition comprising 5-fluorocytosine. In yet another aspect, a method of treating a cancer is provided. The method comprises administering to a subject in need thereof a sufficient amount of an expression vector to induce expression of cytosine deaminase which is capable of converting 5-fluorocytosine to 5-fluorouracil in cells of the cancer and a cancer-treating effective amount of a composition comprising 5-fluorocytosine.

Provided herein are systems, compositions, kits, and methods for the suppression of pain (e.g., chronic pain). Genes encoding ion channels (e.g., SCN9A) responsible for the propagation pain signals in neurons (e.g., DRG neurons) may be edited using a genome editing agent (e.g., a nucleobase editor). In some embodiments, loss-of-function ion channel mutants are generated, leading to pain suppression. In some embodiments, the genome editing agent is administered locally to the site of pain or to the nerves responsible for propagation of the pain signal.

The present invention relates to a vaccine comprising the insertion of three genes, the TAA/ecdCD40L EA1 and CDA, driven by promoters L-plastin/cytosinedeaminase and CMV as a three gene, three transcription unit oncolytic virus as a conditionally replication competent adenoviral vector which replicates only in tumor cells. In these transcription units, the E1A gene of the adenoviral vector as well as the cytosine deaminase gene are under the control of the L-plastin promoter, while the TAA/ecdCD40L transcription unit is under control of a the CMV promoter.

The present disclosure provides for endonuclease enzymes having distinguishing domain features, as well as methods of using such enzymes or variants thereof.