The present invention is directed to chimeric antigen receptor (CAR) compositions and methods of their use in cancer and anti-viral immunotherapy. In particular, the CAR of the invention comprises a costimulatory signal (CSS) domain comprising herpes virus entry mediator protein (HVEM) or a functional fragment or variant thereof. CARs comprising such a HVEM CSS exhibit enhanced effector function.

Recombinant polynucleotides and vectors containing an engineered (artificial) exon-intron-exon gene structure in a transgene are provided, which undergoes splicing when it is expressed in a target cell.

Compositions and methods are provided for treating cancer comprising a composition comprising an oncolytic virus and a targeting moiety on the surface of the virus, wherein the oncolytic virus does not encode or express the targeting moiety within various aspects such compositions and methods can be used to treat a wide variety of cancers (e.g., gastrointestinal cancer, such as esophageal, stomach and colon cancers).

The present invention relates to non-laboratory virus strains, for example of herpes viruses such as HSV, with improved oncolytic and/or gene delivery capabilities as compared to laboratory virus strains.

The present invention provides a herpes virus with improved oncolytic properties which comprises a gene encoding an immunomodulatory cytokine and which lacks a functional ICP34.5 gene and a functional ICP47 encoding gene.

The present invention relates to the discovery of compositions and methods for altering Amyloid Precursor Protein (APP) processing. Alerting APP processing is aids the treatment of neuropathological disorders such as those associated with HIV infection and Alzheimer's disease (AD). The invention includes fusion protein constructs that include an effector protein and an HSV US9 protein or functionally active fragment thereof that reduce the amount of amyloid -protein produced in a cell.

The present invention relates to non-laboratory virus strains, for example of herpes viruses such as HSV, with improved oncolytic and/or gene delivery capabilities as compared to laboratory virus strains.

A delivery system that includes a recombinantly synthesized protein polymer with protease cleavage sites such as matrix metalloproteinase responsive sequences engineered within the protein polymer. The system may be used to treat cancer, wounds, or pathological conditions in other tissues that express excess protease relative to healthy tissue.

The present invention relates to exogenous TAP inhibitor armed oncolytic viruses that replicate selectively in cancer cells, evade CD8+ cytolytic T-cells, and induce the immune system to recognize tumor cells. Preferred viruses of the invention have a heterologous gene that encodes a function that affects antigen presentation by inhibiting TAP. The viruses of the invention also comprise one or more heterologous genes encoding immunomodulatory polypeptides, prodrug converting enzymes, or matrix degrading enzymes. Compositions and therapeutic methods using the oncolytic viruses are also provided, including compositions and therapeutic methods for treating cancers, such as melanoma, head and neck cancer, ovarian cancer, breast cancer, glioblastoma, bladder cancer, prostate cancer, lung cancer, liver cancer, colorectal cancer, pancreatic cancer, and renal cancer.

The present invention relates to exogenous TAP inhibitor armed oncolytic viruses that replicate selectively in cancer cells, evade CD8+ cytolytic T-cells, and induce the immune system to recognize tumor cells. Preferred viruses of the invention have a heterologous gene that encodes a function that affects antigen presentation by inhibiting TAP. The viruses of the invention also comprise one or more heterologous genes encoding immunomodulatory polypeptides, prodrug converting enzymes, or matrix degrading enzymes. Compositions and therapeutic methods using the oncolytic viruses are also provided, including compositions and therapeutic methods for treating cancers, such as melanoma, head and neck cancer, ovarian cancer, breast cancer, glioblastoma, bladder cancer, prostate cancer, lung cancer, liver cancer, colorectal cancer, pancreatic cancer, and renal cancer.