IMMUNOLIPOSOMES FOR TREATMENT OF CANCER

• US 20100239652A1
• Filed: 09/26/2008
• Published: 09/23/2010
• Est. Priority Date: 09/28/2007
• Status: Abandoned Application

• Current Assignee: Universitã¤Tsspital Basel (Universitã¤Tsspital-Basel)
• Original Assignee: Universitã¤Tsspital Basel (Universitã¤Tsspital-Basel)
• Inventors: Mamot, Christoph, Rochlitz, Christoph
• Application Number:
  US12/680,698
• Publication Number:
  US 20100239652A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 47/6913 the liposome being modified on its surface by an antibody
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis

Abstract

The present invention relates to immunoliposomes for multiple treatment of human patients suffering from cancer, particularly a cancer represented by a locally advanced or metastatic tumor and to compositions used in said method. The invention further relates to the use of immunoliposomes for the treatment of multi-drug resistance in cancer therapy.

Claims

1. An immunoliposome comprising an antibody or an antibody fragment, which recognizes and binds to an EGF receptor antigen on the surface of a solid tumor and further encapsulating in the liposome an anti-tumor compound, for multi-line treatment of cancer.

2. An immunoliposome according to claim 1, wherein said tumor is an EGFR-positive tumor.

3. An immunoliposome according to claim 1, wherein the liposome encapsulates a cytostatic compound.

4. An immunoliposome according to claim 1, wherein the antitumor compound is a compound selected from the group consisting of daunomycin, idarubicin, mitoxantrone, mitomycin, a platinum analog, vincristine, epirubicin, aclacinomycin, methotrexate, etoposide, doxorubicin, cytosine arabinoside, a fluorinated pyrimidine, purine, or nucleoside, thiotepa, BCNU, a taxane derivative or isolate, camptothecins, polypeptides, and a nucleic acid.

5. An immunoliposome according to claim 4, wherein the cytotoxic compound is a compound selected from the group consisting of doxorubicin, epirubicin and vinorelbine.

18. A method according to claim 39, wherein the amount of immunoliposome or a pharmaceutical composition in the treatment is such as to exhibit no or substantially no toxic side effects.

19. A method according to claim 39, wherein the treatment is topical and does not show skin toxicity.

20. A method according to claim 39, wherein the treatment does not cause the patient to show palmar plantar erythema.

21. A method according to claim 39, wherein the treatment is topical and shows no or substantially no toxic side effects at a concentration of between 5 mg/m² and 80 mg/m².

22. An immunoliposome according to claim 21, wherein the treatment shows no or substantiality no toxic side effects at a concentration of up to 40 mg/m².

23. An immunoliposome according to claim 1, wherein the antibody or antibody fragment is covalently bound to the liposome membrane.

24. An immunoliposome according to claim 1, wherein the antibody is covalently conjugated to the terminus of a linker molecule anchored to the liposome.

25. An immunoliposome according to claim 24, wherein the linker molecule is a polyethylene glycol.

26. An immunoliposome according to claim 1, wherein the antibody is a monoclonal antibody directed to the ligand-binding extracellular domain of the EGF receptor.

27. A method according to claim 39, wherein the cancer is selected from the group consisting of Kaposi'"'"'s sarcoma, recurrent ovarian cancer, soft tissue sarcoma, glioma, melanoma, mesothelioma, transitional cell carcinoma of the urothelial tract, endometrial, pancreatic, small-cell and non-small-cell lung, hepatocellular, renal cell, esophageal, colorectal, anal, vaginal, vulvar, prostate, basal cell carcinoma of the skin head and neck, and choiangio carcinoma.

28. A method according to claim 39, wherein the cancer is selected from the group consisting of prostate, pancreatic, kidney, urothelial, oesophageal, head and neck, colonrectal, a hepatocellular cancer and a mesothelioma.

29. A method according to claim 39, wherein said patient is suffering from a prostate cancer with a tumor that has progressed on hormonal and/or docetaxel and/or mitoxanthrone treatment.

30. A method according to claim 39, wherein said patient is suffering from a pancreatic cancer with a tumor that has progressed on gemcitabine and/or capecitabine and/or oxaliplatin treatment.

31. A method according to claim 39, wherein said patient is suffering from a kidney cancer with a tumor that has progressed on interferon and/or capecitabine and/or sunitinib and/or sorafinib treatment.

32. A method according to claim 39, wherein said patient is suffering from an esophageal cancer with a tumor that has progressed on cisplatinum and/or 5-FU and/or docetaxel and/or cetuximab treatment.

33. A method according to claim 39, wherein said patient is suffering from a colon and/or rectal cancer with a tumor that has progressed on cetuximab and/or Bevacizumab and/or oxaliplatin and/or irinotecan and/or capecitabine and/or 5-FU treatment.

34. A method according to claim 39, wherein said patient is suffering from a urothelial cancer with a tumor that has progressed on cis- or carboplatinum and/or gemcitabine and/or doxorubicin and/or methotrexate and/or vincristin.

35. A method according to claim 39, wherein said patient is suffering from a mesothelioma with a tumor that has progressed on cis- or carboplatinum and/or gemcitabine and/or pemetrexed.

36. A method according to claim 39, wherein said patient is suffering from a hepatocellular cancer with a tumor that has progressed on sunitinib and/or sorafenib.

37. A method according to claim 39, wherein the cancer represented by is a locally advanced or metastatic tumor, wherein a response rate is achieved of between 5% and 95%.

38. A pharmaceutical composition comprising an immunoliposome according to claim 1 together with a pharmaceutically acceptable carrier or excipient or a diluent for first- to multi-line, particularly for second-line, particularly third-line, particularly fourth-line, particularly fifth-line, particularly sixth-line, particularly seventh- and higher-line treatment of cancer, particularly a cancer represented by a locally advanced or metastatic tumor, particularly an EGFR-positive tumor, in a human patient in a clinical set-up.

39. A method of treatment of cancer in a human patient comprising administering to said human patient an immunoliposome or a pharmaceutical composition according to claim 1.

40. A method according to claim 39, wherein the cancer is a locally advanced or metastatic tumor, and the patient has received, but not responded to, at least one other cancer treatment noliposome or a pharmaceutical composition according to any of the preceding claims.

41. A method according to claim 39, wherein the cancer is an EGFR-positive tumor, in a human patient in a clinical set up.

42. A method according to claim 40, wherein the patient has received, to at least two other cancer.

43. A method according to claim 39, wherein the patient is multi-drug resistant.

45. A method according to claim 39, wherein the cancer is breast cancer.

46. A method according to claim 39, wherein the cancer is colonrectal cancer.

49. A pharmaceutical composition comprising an immunoliposome according to claim 38, wherein said immunoliposome encapsulates doxorubicin and further comprises antibody MAb C225 or antibody EMD72000 or a fragment thereof, which still exhibits the specific binding properties of one or both of said ant

6-17. -17. (canceled)

44. (canceled)

47-48. -48. (canceled)