Methods of treatment and compositions therefor

• US 20050070474A1
• Filed: 04/28/2004
• Published: 03/31/2005
• Est. Priority Date: 04/28/2003
• Status: Abandoned Application

• Current Assignee: Auckland UniServices Limited (Auckland University)
• Original Assignee: Auckland UniServices Limited (Auckland University)
• Inventors: Sun, Xuying, Vale, Molly Frances, Krissansen, Geoffrey Wayne
• Application Number:
  US10/835,545
• Publication Number:
  US 20050070474A1
• Time in Patent Office: Days
• US Class Current: 514/44.R
• CPC Class Codes: A61K 48/005 characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 15/111 General methods applicable to biologically active non-coding nucleic acids
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/12 catalytic nucleic acids, e.g. ribozymes
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2320/31 Combination therapy

Abstract

The present invention concerns the treatment of tumours. In particular the invention concerns the combination of agents which are adapted to increase B7-H3 and agents which are adapted to decrease or inhibit one or more HIFs. In a preferred embodiment, a vector adapted to express B7-H3 is administered along with antisense HIF.

Claims

1. A method of treating tumors in a subject, the method comprising at least the steps of administering:

an effective amount of an agent adapted in use to increase B7-H3; and

,

an effective amount of an agent adapted in use to decrease or inhibit one or more types of HIF.

2. A method as claimed in claim 1 wherein the agent adapted to decrease or inhibit one or more types of HIF is a nucleic acid.

3. A method as claimed in claim 2 wherein the nucleic acid is chosen from the group consisting:

An antisense molecule;

iRNA;

single-stranded DNA;

ribozyme; and

DNAzyme;

4. A method as claimed in claim 1 wherein the agent adapted to decrease or inhibit one or more types of HIF targets HIF alpha subunits.

5. A method as claimed in claim 1 wherein the one or more types of HIF are chosen from the group consisting:

HIF-1α

;

HIF-2α

; and

HIF-3α

.

6. A method as claimed in claim 1 wherein the agent adapted to decrease or inhibit one or more types of HIF is chosen from the group consisting:

antisense HIF-1α

;

antisense HIF-2α

;

antisense HIF-3α

.

7. A method as claimed in claim 3 wherein the agent is a vector adapted to produce such nucleic acids in use.

8. A method as claimed in claim 1 wherein the agent adapted to increase B7-H3 is chosen from the group consisting:

B7-H3 or a functional equivalent thereof; and

a nucleic acid vector adapted to express in use B7-H3 or a functional equivalent thereof.

9. A method as claimed in claim 1 wherein the agents are administered intratumorally.

10. A method as claimed in claim 1 wherein the agents are administered systemically.

11. A method as claimed in claim 1 wherein the agents are administered sequentially in any order.

12. A method as claimed in claim 1 wherein the agents are administered simultaneously.

13. A method as claimed in claim 1 wherein the subject is a mammal.

14. A method as claimed in claim 13 wherein the mammal is a human.

15. A method a method of treating tumours in a subject, the method comprising at least the steps of:

conducting a method as claimed in claim 1;

isolating one or more immune cells from the subject;

expanding the one or more immune cells in vitro;

returning said immune cells to the subject.

16. A method as claimed in claim 15 wherein the one or more immune cells are splenocytes, lymph node lymphocytes, or tumour-infiltrating lympocytes.

17. A method as claimed in claim 15 wherein the immune cells are returned to the subject by injection.

18. A method of treating tumours comprising at least the steps of:

isolating one or more tumour cells from a tumour-bearing subject;

exposing one or more tumour cells with an effective amount of an agent adapted in use to increase B7-H3;

returning the one or more cells to the subject; and

administering to the subject an agent adapted in use to decrease or inhibit one or more types of HIF.

19. A method as claimed in claim 18 wherein the one or more isolated tumour cells are transfected with a nucleic acid vector adapted in use to express B7-H3.

20. A method as claimed in claim 18 wherein the one or more tumour cells are returned to the subject via injection.

21. A method as claimed in claim 18 wherein the method further comprises the step of exposing one or more tumour cells isolated from the subject to an effective amount of an agent adapted in use to decrease or inhibit one or more types of HIF.

22. A composition comprising at least an agent adapted in use to increase B7-H3 and an agent adapted in use to decrease or inhibit one or more types of HIF together with one or more pharmaceutically acceptable carriers, diluents or excipients.

23. A composition as claimed in claim 22 wherein the agent adapted to increase B7-H3 is chosen from the group consisting:

B7-H3 or a functional equivalent thereof; and

a nucleic acid vector adapted to express in use B7-H3 or a functional equivalent thereof.

24. A composition as claimed in claim 22 wherein the agent adapted to decrease or inhibit one or more types of HIF is a nucleic acid.

25. A composition as claimed in claim 24 wherein the nucleic acid is chosen from the group consisting:

An antisense molecule;

iRNA;

single-stranded DNA;

ribozyme; and

DNAzyme.

26. A composition as claimed in claim 22 wherein the agent adapted to decrease or inhibit one or more types of HIF targets HIF alpha subunits.

27. A composition as claimed in claim 22 wherein the one or more types of HIF are chosen from the group consisting:

HIF-1;

HIF-2; and

HIF-3.

28. A composition as claimed in claim 22 wherein the agent adapted to decrease or inhibit one or more types of HIF is chosen from the group consisting:

antisense HIF-1α

;

antisense HIF-2α

;

antisense HIF-3α

.

29. A composition as claimed in claim 25 wherein the agent is a vector adapted to produce such nucleic acids in use.

30. A kit comprising at least:

an agent adapted in use to increase B7-H3; and

separately,

an agent adapted in use to decrease or inhibit one or more types of HIF.