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AssigneeNew York University
InventorsDaniel Meruelo, Christine Pampeno, Alicia Hurtado Martinez
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Provided are polynucleotides and viral vectors, particularly, alphavirus vectors such as Sindbis viral vectors, which encode multiple, e.g., two or more, epitopes of at least one tumor associated antigen in which each epitope is separated by a processing or enzyme cleavage site. The multiple epitopes of the two or more tumor associated antigens encoded by the described polynucleotides and viral vectors may be the same or different. Methods of treating mammalian subjects having a cancer or tumor expressing the tumor associated antigen epitopes are provided, in which the viral vectors encoding the multiple epitopes, as well as other immunostimulatory or immunomodulatory components, generate an anti-cancer or anti-tumor immune response in which high levels of effector T cells increase the survivability of tumored mammalian subjects and result in epitope spreading, thus providing a further enhancement of the immune response.
A polynucleotide encoding an alphavirus protein, or a fragment thereof, and two or more epitopes of one or more tumor associated antigens, wherein each epitope is separated by an enzyme cleavage site.
The polynucleotide of 8, wherein the one or more suicide genes is capable of converting an inert prodrug into a cytotoxic metabolite, and the inert prodrug is selected from the group consisting of ganciclovir, acyclovir, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodouracil (FIAU), 6-methoxypurine arabinoside, and 5-fluorocytosine.
A Sindbis viral vector comprising a polynucleotide encoding two or more epitopes comprising 5-30 amino acids of a tumor associated antigen, wherein each epitope is separated by a furin enzyme cleavage site.
A viral vector pseudotyped with one or more alphavirus envelope proteins, wherein the viral vector comprises a polynucleotide encoding two or more epitopes comprising 5-30 amino acids of a tumor associated antigen, wherein each epitope is separated by an enzyme cleavage site.
Dependencies are inferred from the claim text.