A conditionally replicating adenovirus were generated that can specifically replicate and express therapeutic genes in neuroendocrine tumors. The promoter-specific expression of the adenoviruses is regulated upstream by an INSM1 (insulinoma-associated-1) promoter that is silent in normal adult tissues but active in developing neuroendocrine cells and neuroendocrine tumors. By placing the I NSM 1-promoter with an insulator and two copies of neuronal restrictive silencer elements in an adenoviral vector, the construct can retain tumor specificity and drive expression of a mutated adenovirus E1A gene (Δ24E1A) and the herpes simplex virus thymidine kinase gene. The I NSM1-promoter-driven viruses could replicate specifically in the I NSM1-positive cells and I NSM1-specific HSV-tk expression in combination with ganciclovir treatment displayed dose-dependent tumor cell-specific killing in insulinomas. When the INSM1-promoter driven HSV-tk was combined with Δ24E1A and I NSM 1 p-HSV-tk viruses, the co-infected insulinoma expressed higher levels of HSV-tk and more efficient tumor suppression as compared to the I NSM1 p-HSV-tk virus alone.

The present disclosure relates to a composition for transduction of a virus in a cell by using a crosslinked product of PEGylated magnetic nanoparticles and catechol grafted poly-L-lysine by application of an external magnetic field. When the composition is used, a virus may be delivered into cells more rapidly and efficiently than in intracellular uptake of a virus by CAR-mediated endocytosis.

The present invention is related to the use of a virus, preferably an adenovirus for reversing resistance in cells.

A fast and accurate three-plasmid oncolytic adenovirus recombinant packaging system Ad5MixPlus and an application thereof are provided. The system is composed of three adenovirus recombinant plasmids. The core technology of the system is that two sets of different site recombination sequences are skillfully loaded on a first 5-type adenovirus right arm backbone plasmid large vector, then two small shuttle plasmids respectively provide a right arm-modified Hexon/E3/Fiber sequence and an E1a expression cassette controlled by a left arm tumor-specific promoter, and the difficulties and obstacles to the modification of the adenovirus backbone large vector are overcome. After two rounds of site-specific recombination, the ideal oncolytic adenovirus is packaged accurately and quickly.

Provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of an adenoviral vector with a genetically modified fiber incorporating a Lyp-1 peptide motif and at least one CD122/CD132 agonist and/or an immune checkpoint inhibitor.

Disclosed herein are compositions and methods for treating cancer in a subject. This involves administering an oncolytic virus containing a heterologous DNA sequence encoding one or more immunomodulatory and/or immunostimulatory polypeptide(s) of interest to the subject under conditions effective to enhance an anti-tumor immune response in the subject, and to treat cancer. It also relates to a method of enhancing the delivery to and distribution within a tumor mass of therapeutic viruses.

A therapeutic agent comprising a nucleic acid and a TCR modified immune cell and use thereof. The therapeutic agent comprises a first composition comprising a first active ingredient and a second composition comprising a second active ingredient. The first active ingredient includes or contains a nucleic acid having a labeling polypeptide coding sequence for being introduced into a tumor cell and/or a cancer cell. The labeling polypeptide has one or more epitope polypeptides which can be presented on a surface of the tumor cell and/or cancer cell by MHC class I molecules. The second composition comprises a second active ingredient in a second pharmaceutically acceptable carrier and the second active ingredient comprises a T cell receptor modified immune cell which can specifically recognize and bind to the epitope polypeptide presented by MHC class I molecules. The therapeutic agent achieves synergistic treatment effect and provides a new route for tumor treatment.

In one embodiment, the present invention provides an anti-cancer-associated non-tumor cell agent.

In one embodiment, the present invention relates to an anti-cancer-associated non-tumor cell agent comprising an oncolytic virus comprising a p53 gene. In one embodiment, the present invention relates to an anti-cancer-associated non-tumor cell preparation comprising a recombinant virus comprising: a first gene cassette containing a telomerase reverse transcriptase promoter, an E1A gene, an IRES sequence and an E1B gene; and a second gene cassette containing a promoter and a p53 gene.

The present invention relates to an oncolytic adenovirus capable of co-expressing interleukin-12 and a C-met-inhibiting oligonucleotide; and an antitumor immune-boosting composition and anticancer composition comprising the oncolytic adenovirus. The present invention has first identified an adenovirus system having simultaneous effects of IL-12 expression and C-met inhibition in cancer gene treatment. The adenovirus system of the present invention is capable of inhibiting C-met while expressing interleukin-12, thereby restoring immune functions in a tumor environment to enhance anticancer effects such as the inhibition of tumor recurrence and tumor growth and to inhibit tumor migration. Accordingly, the adenovirus system of the present invention can be effectively used in the treatment of cancer.

The present invention is related to the use of a virus, preferably an adenovirus for reversing resistance in cells.