A chimeric oncolytic virus is described that includes a herpesvirus having a modified nucleic acid sequence, including a modification of the herpesvirus gamma (1)34.5 gene (γ.sub.134.5) or a nucleic acid with at least about 70% homology to the γ.sub.134.5 gene that reduces its expression; a second viral nucleic acid sequence encoding a PKR evasion protein that does not cause virulence; and a third nucleic acid sequence encoding a tumor-associated antigen. Methods of using the chimeric oncolytic virus to treat subjects having cancer, or to vaccinate subjects at risk of developing cancer, are also described.

Methods for passive transfer of immunity using recombinant herpes simplex virus 2 (HSV-2) vaccine vectors, virions thereof, compositions and vaccines comprising such.

Described are improved methods for treating solid tumors, such as malignant gliomas, with a dual approach utilizing a CAR-T immunotherapy and a viral oncolytic therapy.

A malaria vaccine composition is disclosed herein that uses liver-stage parasite exported proteins as the target of a protective immune response instead of sporozoite proteins. Also disclosed is a recombinant viral particle that comprises a fusion protein disclosed herein, wherein the malaria antigen is displayed within the viral particle. Also disclosed is an isolated polynucleotide that comprises a nucleic acid sequence encoding a fusion protein disclosed herein operably linked to an expression control sequence. Also disclosed is a recombinant herpes simplex virus (HSV) genome comprising a modified VP26 gene encoding a fusion protein disclosed herein. Also disclosed is a vaccine composition that comprises a recombinant viral particle disclosed herein in a pharmaceutically acceptable excipient. In some cases, the composition further comprises an adjuvant.

This disclosure provides engineered genetic systems for sequestering and/or destroying viruses, compositions and cells comprising the genetic systems, and methods of treating viral infections, reducing viral load, and/or reducing viral spread. The disclosure also provides libraries comprising elements to be incorporated into the engineered genetic systems.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a cystic fibrosis transmembrane conductance regulator (CFTR) polypeptide (e.g., a human CFTR polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of a chronic lung disease, such as cystic fibrosis); and articles of manufacture or kits thereof.

The present disclosure provides recombinant nucleic acids (e.g., recombinant herpes viral genomes) comprising one or more polynucleotides encoding an antibody; viruses (e.g., herpes viruses) comprising the recombinant nucleic acids; compositions comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for localized, virus-mediated delivery and expression of the encoded antibody); and articles of manufacture or kits thereof.

The present invention relates to oncolytic virus comprising: (i) a GM-CSF-encoding gene; and (ii) an immune co-stimulatory pathway activating molecule or an immune co-stimulatory pathway activating molecule-encoding gene.

A method of enhancing or inducing the expression of the HLA-G molecule by human cells is provided. The method includes administering the human Herpesvirus 6 U94 molecule or a derivative thereof, or a gene expression vector including and expressing the human Herpesvirus 6 U94 gene to a patient in need thereof or to an in vitro cell, tissue, or organ culture.

An oncolytic virus for use in a method of treating or preventing cutaneous squamous cell carcinoma (CSCC), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), small cell lung cancer (SCLC), advanced recurrent head and neck cancer, squamous cell carcinoma of the head and neck (SCCHN), nasopharyngeal carcinoma (NPC), hepatocellular carcinoma (HCC), anal cancer, colorectal cancer (CRC), basal cell carcinoma (BCC), Merkel cell carcinoma, appendiceal carcinoma, sarcoma of the skin, recurrent melanoma after surgery, advanced or metastatic urothelialcarcinoma, liver metastases, microsatellite instability high cancer (MSI-H), mixed advanced solid tumors, virally caused cancer, locoregionally advanced cancer, pediatric cancer, cancer in patients with no or minimal pre-existing anti-cancer immunity, cancer as first line therapy, cancer in previously treated patients, cancer in patients who have not received checkpoint blockade therapy, and/or cancer in patients who have received checkpoint blockade therapy, wherein the oncolytic virus: is, or is derived from, a clinical isolate which has been selected by comparing the abilities of a panel of three or more clinical isolates of the same viral species to kill tumor cells of two or more tumor cell lines in vitro and selecting a clinical isolate which is capable of killing cells of two or more tumor cell lines more rapidly and/or at a lower dose in vitro than one or more of the other clinical isolates in the panel; comprises (i) a fusogenic protein-encoding gene; and (ii) an immune stimulatory molecule or an immune stimulatory molecule-encoding gene; comprises (i) a GM-CSF-encoding gene; and (ii) an immune co-stimulatory pathway activating molecule or an immune co-stimulatory pathway activating molecule-encoding gene; and/or comprises a gene encoding a CTLA-4 inhibitor.