Fiber-modified adenoviral vectors for enhanced transduction of tumor cells

• US 20060062764A1
• Filed: 08/11/2005
• Published: 03/23/2006
• Est. Priority Date: 08/25/2004
• Status: Abandoned Application

• Current Assignee: Cell Genesys Incorporated (ANI Pharmaceuticals, Inc.)
• Original Assignee: Cell Genesys Incorporated (ANI Pharmaceuticals, Inc.)
• Inventors: Ganesh, Shanthi, Yu, DeChao, Police, Seshidar-Reddy
• Application Number:
  US11/201,384
• Publication Number:
  US 20060062764A1
• Time in Patent Office: Days
• US Class Current: 424/93.200
• CPC Class Codes: A61K 2039/5152 Tumor cells
• CPC Class Codes: A61K 35/13 Tumour cells, irrespective of tissue of origin tumour vaccines A61K39/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/10322 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/10345 Special targeting system for viral vectors
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

Adenoviral vectors which effectively transduce primary tumor cells are provided. The adenoviral vectors comprise a chimeric adenovirus fiber protein which includes at least a portion of a Subgroup C adenovirus fiber shaft and at least a portion of a Subgroup B adenovirus or serotype 37 adenovirus head, wherein the head region binds CD46.

Claims

1. A method of expressing a heterologous nucleic acid in a primary tumor cell comprising transducing said primary tumor cell with an adenovirus vector comprising a chimeric fiber protein wherein said chimeric fiber protein comprises at least a portion of a Subgroup C adenovirus shaft region and at least a portion of the head region of a Subgroup B adenovirus, wherein the head region binds CD46.

2. The method of claim 1, wherein said chimeric fiber protein comprises at least a portion of an Ad5 or Ad2 shaft and at least a portion of an Ad35 head.

3. The method of claim 1, wherein the cell is transduced in vitro.

4. The method of claim 1, wherein the cell is transduced in vivo.

5. The method of claim 1, wherein the chimeric fiber protein comprises from about amino acids 46 to 136 of SEQ ID NO:

6.

6. The method of claim 1, wherein the chimeric fiber protein comprises from about amino acids 47 to 399 of SEQ ID NO:

2 or amino acids 47 to 399 of SEQ ID NO;

4.

7. The method of claim 5, wherein the chimeric fiber protein, comprises from about amino acids 47 to 399 of SEQ ID NO:

2 or amino acids 47 to 399 of SEQ ID NO;

4.

8. The method of claim 1, wherein said primary tumor cell is a cell selected from the group consisting of a lung tumor cell, a prostate tumor cell, a head and neck tumor cell, a bladder tumor cell and a kidney tumor cell.

9. The method of claim 1, wherein said primary tumor cell is a non-small cell lung tumor cell.

10. The method of claim 1, wherein said adenovirus preferentially replicates in said primary tumor cells.

11. The method of claim 10, wherein said adenovirus comprises a heterologous transcriptional regulatory element (TRE) operatively linked to at least one adenoviral coding sequence that is essential for replication.

12. The method of claim 11, wherein said TRE is selected from the group consisting of a cell-specific TRE, a cell-status specific TRE and a tissue-specific TRE.

13. The method of claim 11, wherein said TRE is selected from the group consisting of a PSA TRE, an E2F TRE, a telomerase (TERT) TRE, an urokinase plasminogen activator (uPA) TRE, a probasin TRE, a tyrosinase related protein-2 TRE, a MART-1 TRE, a CRGL2 TRE and a PRL-3 protein tyrosine phosphatase TRE.

14. The method of claim 11, wherein said adenoviral coding sequence is in an adenoviral coding region selected from the group consisting of E1a, E1b, E2a, E2b and E4.

15. The method of claim 10, wherein said adenovirus comprises a deletion of part or all of the E1B 19-kDa region.

16. The method of claim 1, wherein said adenovirus comprises a deletion of an adenoviral coding sequence essential for replication.

17. The method of claim 16, wherein said adenovirus is replication incompetent in the primary tumor cell.

18. The method of claim 17, wherein said adenoviral coding sequence essential for replication is selected from the group consisting of E1a, E1b, E2a, E2b and E4.

19. The method of claim 1, wherein said adenovirus comprises a deletion of at least one adenoviral E3 coding sequence.

20. The method of claim 19, wherein said adenoviral E3 coding sequence is selected from the group consisting the coding sequences for the 19K, 14.7K, 14.5K, 12.5K, 11.6K, 10.4K and 6.7K E3 proteins.

21. The method of claim 19, wherein all of the E3 coding sequences are deleted.

22. The method of claim 19, wherein said adenovirus comprises the 10.4K, 14.5K and 14.7K E3 coding sequences.

23. The method of claim 1, wherein said adenovirus comprises all of the native E3 coding sequences.

24. The method of claim 1, wherein said adenovirus comprises a GM-CSF coding sequence operatively linked to regulatory elements wherein GM-CSF is expressed in said primary tumor cell.

25. The method of claim 24, wherein said GM-CSF coding sequence is a human sequence.

26. The method of claim 24, further comprising inactivating the transduced tumor cell and administering the transduced primary tumor cell to a mammal.

27. The method of claim 26, wherein said tumor cell is autologous for said mammal.

28. The method of claim 26, wherein said tumor cell is allogeneic for said mammal.

29. The method of claim 26, wherein said mammal contains tumor cells of the same type as the transduced tumor cells.

30. The method of claim 29, wherein said mammal is a human.