Replication defective adenovirus vector in vaccination
View Patent ↗Methods for generating immune responses using adenovirus vectors that allow multiple vaccinations with the same adenovirus vector and vaccinations in individuals with preexisting immunity to adenovirus are provided.
1. A method of treating a carcinoembryonic antigen (CEA)-expressing cancer in a human in need thereof, the method comprising: administering to the human a single dose of a pharmaceutical composition comprising from 1×10 9 to 5×10 11 viral particles of a replication-defective vector comprising a nucleic acid sequence encoding a modified carcinoembryonic antigen (CEA) comprising a sequence set forth in SEQ ID NO:5 (YLSGADLNL).
2. The method of claim 1 , wherein the human has tumor cells that overexpress CEA as compared with a baseline level in a non-tumor cell.
3. The method of claim 1 , wherein the human has pre-existing immunity to Ad5.
4. The method of claim 1 , wherein the human has cancer of the colon, rectum, breast, lung, pancreas, thyroid, prostate, or a combination thereof.
5. The method of claim 1 , wherein the replication-defective vector is a replication-defective adenoviral vector.
6. The method of claim 5 , wherein the replication-defective adenoviral vector has a deletion in an early 2b (E2b) gene region.
7. The method of claim 6 , wherein the replication-defective adenoviral vector further comprises a deletion in an early 1 (E1) gene region, a deletion in an early 3 (E3) gene region, a deletion in an early 4 (E4) gene region, or a combination thereof.
8. The method of claim 1 , wherein the replication-defective vector comprises a nucleic acid sequence with at least 80% identity to a region in SEQ ID NO: 3 from 1057 to 3165.
9. The method of claim 1 , wherein the pharmaceutical composition comprises a dose of at least 10 9 replication-defective viral particles.
10. The method of claim 1 , wherein the pharmaceutical composition comprises a dose of at least 10 11 replication-defective viral particles.
11. The method of claim 1 , wherein the administering is subcutaneous administration.
12. The method of claim 1 , wherein the administering is intradermal, parenteral, intravenous, intramuscular or intraperitoneal administration.
13. The method of claim 1 , wherein the human has previously been determined to overexpress CEA in tumor cells as compared with a baseline level in a non-tumor cell.
14. The method of claim 1 , further comprising irradiating the human or administering a chemotherapy to the human.
15. The method of claim 1 , wherein the pharmaceutical composition is administered to the human at least two times.
16. The method of claim 1 , wherein the pharmaceutical composition is administered to the human at an interval of at least two to four weeks or at least three months.
17. The method of claim 1 , wherein the pharmaceutical composition is first administered to the human at an interval of at least two to four weeks followed by a subsequent administration of the pharmaceutical composition at an interval of at least three months.
18. The method of claim 1 , wherein the pharmaceutical composition further comprises an immune adjuvant.
19. The method of claim 1 , further comprising administering to the human a chemotherapy concurrently with or subsequently after administering the pharmaceutical composition.
20. The method of claim 19 , wherein the chemotherapy is selected from the group consisting of FOLFOX, pazopanib, sorafenib, oxaliplatin, bevacizunab, Capecitabine, fluoropyrimidine, irinotecan, Mitomycin, Regorafenib, cetuxinab, panitumumab, acetinophen, and a combination thereof.
21. The method of claim 1 , wherein the pharmaceutical composition further comprises a vector encoding an antigen selected from the group consisting of p53, HPV E6, HPV E7, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, BAGE, DAM-6, -10, GAGE-1, -2, -8, GAGE-3, -4, -5, -6, -7B, NA88-A, NY-ESO-1, MART-1, MC1R, Gp100, PSA, PSM, Tyrosinase, TRP-1, TRP-2, ART-4, CAMEL, Cyp-B, Her2/neu, hTERT, hTRT, iCE, MUC1, MUC2, PRAME, P15, RU1, RU2, SART-1, SART-3, WT1, AFP, 13-catenin/m, Caspase-8/m, CEA, CDK-4/m, ELF2M, GnT-V, G250, HSP70-2M, HST-2, KIAA0205, MUM-1, MUM-2, MUM-3, Myosin/m, RAGE, SART-2, TRP-2/INT2, 707-AP, Annexin II, CDC27/m, TPI/mber-abl, ETV6/AML, LDLR/FUT, Pml/RARa, and TEL/AML1, and a combination thereof.
22. The method of claim 1 , wherein the pharmaceutical composition further comprises a vector encoding an antigen selected from the group consisting of HPV E6, HPV E7, Her2/neu, MUC1, PSA, PSM, or a combination thereof.