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AssigneeVAXum, LLC
InventorsAlbert B. Deisseroth, Lixin Zhang
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Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which enocodes the E6 or E7 protein of HPV. The immunity generated is long term.
An adenoviral expression vector for generating immunity against a tumor antigen, said vector comprising a transcription unit encoding a polypeptide, said polypeptide comprising from the amino terminus a secretory signal sequence, a tumor antigen, and a CD40 ligand, wherein said tumor antigen is different from said CD40 ligand and wherein said CD40 ligand is missing all or substantially all of the transmembrane domain rendering the CD40 ligand secretable, and wherein said polypeptide is adapted to promote Class I MHC restricted cytotoxic T cell lymphocytes (CTLs).
An adenoviral expression vector for generating immunity against a tumor antigen, said vector comprising a transcription unit encoding a fusion protein adapted to promote a Class I MHC restricted CTLs, the fusion protein comprising from the amino terminus a secretory signal sequence, a tumor antigen and a CD40 ligand, wherein said tumor antigen is different from the CD40 ligand and where the CD40 ligand is missing all or substantially all of the transmembrane domain rendering the CD40 ligand secretable, said vector adapted to cause secretion of quantities of tumor antigen/CD40 ligand fusion proteins sufficient to induce a restricted cellular immune response, said CD40 ligand adapted to bind to CD40 on dendritic cells leading to dendritic cell activation and presentation of tumor antigens on Class I MHC of the dendritic cells and migration of the dendritic cells to lymph nodes to induce the amplification of antigen specific CD8+ effector T cells leading to killing of cancer cells positive for the tumor antigen.
Dependencies are inferred from the claim text.