Carcinoembryonic antigen (CEA) peptides
The present invention relates to novel modified CEA agonist (or antagonist) peptides, polypeptides and proteins containing a modified epitope therein, nucleic acids coding therefor, vectors comprising said nucleic acids, mixtures and compositions of the aforementioned agents, and their advantageous use in generating CEA-specific immune responses and/or in the treatment of cancers and the present invention further relates to the foregoing combined with one or more costimulatory molecules.
1 . A CEA agonist polypeptide comprising a modified epitope of CEA, wherein said modified epitope contains the sequence YLSGADLNL (SEQ ID NO: 24).
2 . The CEA agonist polypeptide of claim 1 having the sequence of SEQ ID NO: 46 ( FIG. 62 ).
3 . A nucleic acid comprising a nucleic acid sequence which encodes the CEA agonist polypeptide of claim 1 .
4 . The nucleic acid of claim 2 comprising the sequence of SEQ ID NO: 45 ( FIG. 62 ).
5 . The nucleic acid of claim 3 wherein the nucleic acid is selected from the group consisting of viral nucleic acid, bacterial DNA, plasmid DNA, naked/free DNA, and RNA.
6 . The nucleic acid of claim 5 wherein the viral nucleic acid is selected from the group consisting of adenoviral, alphaviral, and poxviral nucleic acid.
7 . The poxviral nucleic acid of claim 6 , wherein said nucleic acid is selected from the group consisting of avipox, orthopox, and suipox nucleic acid.
8 . The poxviral nucleic acid of claim 7 , wherein said nucleic acid is selected from the group consisting of vaccinia, fowlpox, canary pox and swinepox.
9 . The poxviral nucleic acid of claim 7 , wherein said nucleic acid is selected from the group consisting of TROVAC, NYVAC, ALVAC, MVA, Wyeth, and Poxvac-TC.
10 . The nucleic acid of any one of claim 1 , further comprising a nucleic acid sequence encoding at least one member selected from the group comprising cytokines, lymphokines, and co-stimulatory molecules.
11 . A vector comprising the nucleic acid of claim 1 .
12 . The vector of claim 11 , wherein said vector is selected from the group consisting of recombinant viruses and bacteria.
13 . The recombinant virus vector of claim 12 , selected from the group consisting of adenovirus, alphavirus and poxvirus.
14 . The poxvirus of claim 13 , selected from the group consisting of avipox, orthopox, and suipox.
15 . The poxvirus of claim 13 , selected from the group consisting of vaccinia, fowlpox, canary pox, and swinepox.
16 . The poxvirus of claim 14 , selected from the group consisting of TROVAC, NYVAC, ALVAC, MVA, Wyeth, and Poxvac-TC.
18 . The vector of claim 11 further comprising a nucleic acid sequence encoding at least one member selected from the group consisting of cytokines, lymphokines, and co-stimulatory molecules.
19 . A cell comprising a nucleic acid according to claim 1 wherein the cell expresses a CEA agonist polypeptide.
20 . A method of inhibiting a CEA epitope expressing carcinoma cell in a patient comprising administering to said patient an effective amount of the CEA agonist polypeptide according to claim 1 .
21 . The polypeptide of claim 1 , wherein said polypeptide is purified.
22 . The polypeptide of claim 21 , wherein said polypeptide is comprised in a sterile pharmaceutical composition.
23 . The vectore of claim 11 , wherein said vector is a CEA/TRICOM vector.