Advaxis, Inc.

Merck Sharp + Dohme Corp.

Robert Petit

Michael F Princiotta

Anu Wallecha

David J Mauro

Rodolfo Fleury Perini

David Balli

Brandon Coder

Rodolfo F Perini

Provided herein are recombinant fusion polypeptides comprising one or more antigenic peptides (e.g., fused to a PEST-containing peptide) from cancer-associated proteins. The antigenic peptides can comprise one or more or all of an antigenic peptide comprising a recurrent cancer mutation, an antigenic peptide comprising a heteroclitic mutation, or an antigenic peptide fused to a ubiquitin protein. For example, provided herein are recombinant fusion polypeptides comprising two or more antigenic peptides (e.g., fused to a PEST-containing peptide), wherein each antigenic peptide comprises a recurrent cancer mutation, and wherein at least two of the antigenic peptides are fragments of the same cancer-associated protein. Also provided are nucleic acids encoding such fusion polypeptides, recombinant bacteria orstrains comprising such fusion polypeptides or such nucleic acids, and cell banks comprising such recombinant bacteria orstrains. Also provided herein are methods of generating such fusion polypeptides, such nucleic acids, and such recombinant bacteria orstrains. Also provided are immunogenic compositions, pharmaceutical compositions, and vaccines comprising such fusion polypeptides, such nucleic acids, or such recombinant bacteria orstrains. Also provided are methods of inducing an anti-tumor-associated-antigen immune response in a subject, methods of inducing an anti-tumor or anti-cancer immune response in a subject, methods of treating a tumor or cancer in a subject, methods of preventing a tumor or cancer in a subject, and methods of protecting a subject against a tumor or cancer using such recombinant fusion polypeptides, nucleic acids, recombinant bacteria orstrains, immunogenic compositions, pharmaceutical compositions, or vaccines.

Immunogenic compositions targeting recurrent cancer mutations and methods of use thereof

This disclosure provides compositions, includingdelivery vectors comprising minigene expression constructs, and methods of using the same for inducing an immune response against an antigen-expressing tumor and for treating the same, and vaccinating against the same in subjects bearing the tumors.

Listeria-based compositions comprising a peptide minigene expression system and methods of use thereof

The present invention provides methods of treating, protecting against and inducing an immune response against a tumor or cancer, comprising the step of administering to a subject a recombinantstrain. In one embodiment the present invention relates to a recombinantstrain, said recombinantstrain comprising a recombinant nucleic add, said nucleic add comprising a first open reading frame encoding a recombinant polypeptide comprising a first N-terminal fragment of an LLO protein fused to a heterologous antigen or fragment thereof, and wherein said recombinant nucleic add further comprises a second open reading frame encoding a mutant PrfA protein.

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This invention provides methods and compositions for using evaluating biomarker expression in a disease and providing a multi-targeted-based immunotherapeutic approach against said disease. In a related aspect, the invention relates to a method of treating a disease in a subject, the method comprising the steps of: a. obtaining a biological sample from said subject; b. evaluating the expression of a predetermined number of biomarkers in said biological sample; c. administering to said subject a composition comprising a recombinantstrain, said strain comprising a nucleic acid sequence encoding at least one fusion protein, wherein said fusion protein comprises a biomarker identified in said biological sample, wherein said biomarker is associated with said disease, wherein said biomarker is fused to a PEST-containing polypeptide, and wherein each fusion protein within saidcomprises a different biomarker, thereby treating said disease in said subject.

Biomarker directed multi-target immunotherapy

The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and abased strain that expresses prostate-tissue specific antigen (PSA), and the use of the combination therapies for the treatment of prostate cancer.

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Newtown, PA, United States of America

Robert Petit