The disclosure relates to prostate neoantigens, polynucleotides encoding them, vectors, host cells, recombinant virus particles, vaccines comprising the neoantigens, proteinaceous molecules binding the prostate neoantigens, and methods of making and using them.

An isolated monoclonal antibody or antigen-binding fragment that specifically binds to stage-specific embryonic antigen 4. The monoclonal antibody or antigen-binding fragment includes a heavy-chain CDR1 having the sequence of SEQ ID NO: 33 or SEQ ID NO: 40, a heavy-chain CDR2 having the sequence of SEQ ID NO: 34 or SEQ ID NO: 39, a heavy-chain CDR3 having the sequence of SEQ ID NO: 35 or SEQ ID NO: 41, a light-chain CDR1 having the sequence of SEQ ID NO: 36 or SEQ ID NO: 42, a light-chain CDR2 having the sequence of SEQ ID NO: 37 or SEQ ID NO: 43, and a light-chain CDR3 having the sequence of SEQ ID NO: 38 or SEQ ID NO: 44. Also disclosed is an anti-tumor method carried out by administering the above monoclonal antibody or antigen-binding fragment to a subject having a tumor that expresses stage-specific embryonic antigen 4. Further provided are nucleic acids encoding the above sequences and recombinant cells containing the nucleic acids.

Systems and methods are presented that allow for selection of tumor neoepitopes that are then used to generate recombinant nucleic acids that encode one or more polytopes that are optimized for proper trafficking and processing. In preferred methods, the polytopes are encoded in a plasmid and/or a viral expression system for use as a therapeutic agent.

The disclosed compositions and methods provide an approach for the rational development of a nucleic acid vaccine. Methods are disclosed to deliver a viral genome, and/or a representative or derivative of such, that is attenuated but can, when co-delivered with unreplicable compensatory translational tools to a host cell, initially generate phenotypically wild-type, genetically attenuated viruses which infect subsequent cells and elicit a relevant and robust immune response. However, progeny of this initial generation, lacking the compensatory tools delivered to the initial host cells, are both phenotypically and genetically attenuated, thereby compromised in their ability to induce disease.

The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36 (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).

The present invention is based, in part, on the identification of novel biomarkers, and methods of modulation thereof, for sensitizing cancer cells to T cell-mediated killing.

The invention relates to an immunogenic or vaccine composition against the 2019 novel coronavirus (SARS-CoV-2), comprising a nucleic acid construct encoding a SARS-CoV-2 coronavirus Spike (S) protein antigen or a fragment thereof comprising the receptor-binding domain, wherein the nucleic acid construct sequence is codon-optimized for expression in human.

The disclosure relates to HSV glycoprotein B and HSV glycoprotein C antigenic peptide constructs, HSV protein vaccines, and HSV DNA vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

The present disclosure relates to the use of nucleic acid (e.g., mRNA) combination therapies for the treatment of cancer. The disclosure provides compositions, and methods for their preparation, manufacture, and therapeutic use, wherein those compositions comprise at least two polynucleotides (e.g., mRNAs) in combination wherein the at least two polynucleotides are selected from the group consisting of (i) a polynucleotide encoding an immune response primer (e.g., IL23), (ii) a polynucleotide encoding an immune response co-stimulatory signal (e.g., OX40L), (iii) a polynucleotide encoding a checkpoint inhibitor (e.g., an anti CTLA-4 antibody), and, (iv) a combination thereof. The therapeutic methods disclosed herein comprise, e.g., the administration of a combination therapy disclosed herein for the treatment of cancer, e.g., by reducing the size of a tumor or inhibiting the growth of a tumor, in a subject in need thereof. In some aspects, the combination therapies disclosed herein disclosed are administered intratumorally.

Systems and methods are presented that allow for selection of tumor neoepitopes that are then used to generate recombinant nucleic acids that encode one or more polytopes that are optimized for proper trafficking and processing. In preferred methods, the polytopes are encoded in a plasmid and/or a viral expression system for use as a therapeutic agent.