Mucin antigen vaccine
Provided are expression vectors for generating an immune response to a mucin. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal, a mucin antigen and CD40 ligand. Also provided are methods of generating an immune response against cells expressing a mucin by administering an effective amount of the vector. Further provided are methods of generating an immune response against cancer cells expressing a mucin in an individual by administering an effective amount of the vector. Still further provided are methods of overcoming anergy to a mucin self antigen by administering an effective amount of the vector.
1. A plasmid expression vector for generating in an individual immunity against one or more mucin antigens, said vector comprising a transcription unit, said transcription unit comprising a nucleic acid operably linked to a promoter, said transcription unit encoding a secretable polypeptide, said encoded polypeptide comprising from the amino terminus, a secretory signal sequence, one or more mucin antigen(s) or fragments thereof, and a CD40 ligand, wherein the one or more mucin antigen(s) or fragments thereof are connected together, wherein (i) the one or more mucin antigen(s) or fragments thereof and the CD40 ligand lack all or substantially all of their transmembrane domains; (ii) one end of the connected, one or more mucin antigen(s) or fragments thereof is attached to the amino terminus of the extracellular domain of said CD40 ligand; and, (iii) said encoded polypeptide is configured to promote presentation on Class I MHC and activation with expansion of mucin-specific, Class I MHC restricted, cytotoxic T lymphocytes.
2. A plasmid expression vector according to claim 1 , wherein a liposome is used as a delivery vehicle for said expression vector.
3. An expression vector for generating in an individual immunity against a mucin antigen, said vector comprising a transcription unit encoding a secretable polypeptide, said encoded polypeptide comprising from the amino terminus, a secretory signal sequence, the mucin antigen, and CD40 ligand, wherein (i) the mucin antigen is missing all or substantially all of the transmembrane domain; (ii) the CD40 ligand is missing all or substantially all of the transmembrane domain; (iii) the mucin antigen is attached to the amino-terminus of the extracellular domain of said CD40 ligand; and (iv) wherein said encoded polypeptide is configured to promote presentation of Class I MHC and activation with expansion of mucin-specific, Class I MHC restricted, cytotoxic lymphocytes, and wherein said expression vector is present in a liposome for delivering said expression vector.