Viral vectors are provided for use as genetic immunotherapeutic agents, including preventive and therapeutic vaccines as well as compositions to enhance cellular immune responses and innate immune responses. The vectors are particularly useful for treating or preventing cancer and infectious diseases. The vectors include lentiviral vectors that encode one or more antigens, a combination of adjuvants, and optionally may encode one or more soluble and secreted checkpoint inhibitor molecules. The adjuvants include latent membrane protein 1 (LMP1) from Epstein Barr virus and a fusion protein including LMP1 with in which the intracytoplasmic domain has been replaced by human IPS1 or a variant thereof capable of activating the STING pathway. The vector-encoded sequences are codon optimized for human expression.

The disclosure provides immunogenic cells expressing LMP1, and use thereof in activating T cells and treating cancer. Also provided are methods of producing the immunogenic cells.

Drug-inducible, tunable, and multiplexable Clustered Regularly Interspaced Short Palindromic Repeats from Prevotella and Francisella 1 (Cpf1)-based activators, and methods of use thereof.

The present invention relates to the filed of immunotherapy, in particular, of Epstein-Barr virus-associated diseases (EBV, also designated Human gammaherpesvirus 4), e.g., cancer or post-transplant lymphoproliferative disease, in particular, to adoptive T cell therapy or T cell receptor (TCR) gene therapy. The invention provides a combination of nucleic acids encoding at least two TCR constructs, or the respective proteins or host cells, wherein each TCR construct is capable of specifically binding to its respective epitope in the context of the respective MHC I, and wherein the epitopes are peptides from different antigens expressed by the same infective agent or cancer, e.g., EBV antigens. The invention also provides specific nucleic acids encoding a TCR alpha chain construct (TRA) and/or a TCR beta chain construct (TRB) of a TCR construct specific for an epitope in complex with a human MHC I, wherein the epitope is an epitope of an Epstein-Barr-virus protein, wherein the TCR constructs are specific for epitopes from LMP2A, LMP1 or EBNA3C. Proteins encoded by said nucleic acids, corresponding host cells and pharmaceutical compositions and kits are also objects of the invention.

The presently disclosed subject matter provides methods, reporter gene constructs, and kits for using prostate-specific membrane antigen (PSMA) as an imaging reporter to image a variety of cells and tissues.

The present invention is drawn to compositions and methods to enhance an immune response in order to prevent or treat infections or hyperproliferative diseases such as cancer. More particularly, the composition is an immunostimulatory intracellular signaling peptide fused directly or indirectly to a peptide that leads to multimerization into complexes of three or more units, where the intracellular signaling peptide must be present in a complex of three or more units in order to stimulate an immune response. Inserting this fusion construct into viruses like HIV-1 or introducing it into dendritic cells or tumor cells is predicted to lead to a positive therapeutic effect in humans, non-human mammals, birds, and fish.

The disclosure provides immunogenic cells expressing LMP1, and use thereof in activating T cells and treating cancer. Also provided are methods of producing the immunogenic cells.

Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing a chimeric antigen receptor (CAR) and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

The invention relates to stabilised pre-fusion conformation Class III fusion proteins. The inve ntion also provides vaccine compositions for immunising a subject against viral infections.

Amyloid precursor protein (APP) dysfunction is a key feature in Alzheimer's disease (AD). The sortilin-related receptor 1 (SORLA) functions as a chaperone protein to APP and has reduced expression in AD brains. The APP and SORLA dysfunction results in homeostasis destabilization. Herpesviruses are suspected to be involved in AD pathogenesis. Using a strategic nucleotide BLAST to query SORL1 and APP nucleotide alignment on all Herpesviridae genomes identified similarity sequences from the Epstein-Barr virus and herpes simplex virus 2. The invention describes a treatment to alleviate EBV and HSV2-mediated neurodegeneration by delivering antisense oligonucleotides sequences that target the EBV and HSV2 non-coding sequences to block SORLA and APP disruption. The invention further describes methods to eradicate EBV infection by delivering inducible expression of antisense oligonucleotides targeting EBV genes or an inducible CRISPR/Cas gene-editing system, together with an expression construct encoding anti-apoptotic proteins or with anti-apoptotic proteins for the prevention of cell-mediated apoptosis.