Novel therapeutic processes for treating infectious agents by training or adoptive transfer of immune cells, and useful compositions therefor

• US 20050260226A1
• Filed: 12/08/2003
• Published: 11/24/2005
• Est. Priority Date: 04/27/2000
• Status: Abandoned Application

• Current Assignee: Enzo Therapeutics Incorporated (Enzo Biochem Incorporated)
• Original Assignee: Enzo Therapeutics Incorporated (Enzo Biochem Incorporated)
• Inventors: Donegan, James J., Ilan, Yaron, Rabbani, Elazar, Engelhardt, Dean L., Gotsman, Israel
• Application Number:
  US10/470,601
• Publication Number:
  US 20050260226A1
• Time in Patent Office: Days
• US Class Current: 424/204.100
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2039/5152 Tumor cells
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/0005 Vertebrate antigens from snakes A61K39/38
• CPC Class Codes: A61K 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/292 Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
• CPC Class Codes: A61K 39/461 characterised by the cell type used
• CPC Class Codes: A61K 39/464499 Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor
• CPC Class Codes: A61K 39/464838 Viral antigens
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C12N 2730/10134 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

This invention provides novel processes for therapeutic applications, including the treatment of subjects carrying infectious agents or having impaired autoimmunity or impaired immune condition. The therapeutic applications disclosed herein are also directed at the treatment of cancerous subjects with malignant tumors containing cancerous cells or malignant or cancerous cells. Vaccination processes for preventing infections in subjects are also provided. The novel processes comprise introducing into or adminstering to a subject one or more antigens, or trained or adopted immune cells. These antigens or immune cells are capable of establishing or increasing at least one first specific immune response and decreasing at least one second specific immune response. Such responses include components, such as cellular immune reaction elements, humoral immune reaction elements and cytokines, the latter also encompassing interferons and lymphokines. Useful compositions are also provided by this invention.

Claims

1. A process of treating a subject carrying an infectious agent, said process comprising the steps of:

(a) introducing into or administering to said subject one or more antigens, said antigen or antigens being capable of;

(1) establishing or increasing at least one first specific immune reaction directed against;

(i) said infectious agent;

or

(ii) cells infected with said infectious agent;

or

(iii) a combination of (1)(i) and (1)(ii) above; and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction (a)(1), said second specific immune reaction being directed toward;

(i) said infectious agent;

or

(ii) cells infected with said infectious agent;

or

(iii) uninfected cells;

or

(iv) a combination of any of (2)(i), (2)(ii) and (2)(iii) above.

2. The process according to claim 1, wherein said first specific immune reaction and said second specific immune reaction are directed to at least two different epitopes on said one or more antigens.

3. The process according to claim 1, wherein said first specific immune reaction and said second specific immune reaction are mediated by different components of said subject'"'"'s immune system.

4. The process according to claim 1, wherein said first specific immune reaction and said second specific immune reaction are directed to at least two different epitopes on said one or more antigens and are mediated by different components of said subject'"'"'s immune system.

5. The process according to claim 3, wherein said first specific immune reaction and said second specific immune reaction are directed to the same epitope of said one or more antigens.

6. The process according to claims 4 or 5, wherein said different components of the first specific immune reaction and the second specific immune reaction are selected from the group consisting of cellular immune reaction elements, humoral immune reaction elements and cytokines.

7. The process according to claim 6, wherein when said component or components of the specific immune reaction comprise cellular immune response elements, said corresponding component or components of the specific immune reaction comprise humoral immune response elements or cytokines.

8. The process according to claim 6, wherein when said component or components of the specific immune reaction comprise humoral immune response elements, said corresponding component or components of the specific immune reaction comprise cellular immune response elements or cytokines.

9. The process according to claim 6, wherein when said component or components of the specific immune reaction comprise cytokines, said corresponding component or components of the specific immune reaction comprises cellular immune response elements or humoral immune response elements.

10. The process according to claim 1, wherein said one or more antigens are introduced or administered in a single dose.

11. The process according to claim 1, wherein said one or more antigens are introduced or administered in multiple doses.

12. The process according to claim 1, wherein said one or more antigens are introduced or administered in different dosages.

13. The process according to claim 12, wherein said one or more antigens comprise antigens having different epitopes.

14. The process according to claim 1, wherein said one or more antigens are introduced or administered continuously.

15. The process according to claim 1, wherein said one or more antigens are introduced or administered intermittently or periodically.

16. The process according to claim 1, wherein said one or more antigens are introduced or administered by a single route.

17. The process according to claim 1, wherein said one or more antigens are introduced or administered by at least two different routes.

18. The process according to claim 1, wherein said one or more antigens are introduced or administered by a route selected from the group consisting of oral, intravenous, parenteral, transdermal, subcutaneous, intravaginal, intranasal, mucosal, sublingual, aural, intrabronchial, topical, intramuscular, intraperitoneal, rectal, and combinations of any of the foregoing.

19. The process according to claim 1, wherein said one or more antigens are introduced or administered orally.

20. The process according to claim 1, further comprising introducing or administering one or more carriers.

21. The process according to claim 1, wherein said infectious agent comprises a virus.

22. The process according to claim 20, wherein said virus is selected from the group consisting of HBV, HCV, HIV and a combination of any of the foregoing.

23. A process of treating a subject carrying an infectious agent, said process comprising the steps of:

(a) introducing into or administering to said subject at least two different antigens, each of said antigens being capable of;

(1) establishing or increasing at least one first specific immune reaction directed against;

(i) said infectious agent;

or

(ii) cells infected with said infectious agent;

or

(iii) a combination of (1)(i) and (1)(ii) above; and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction (a)(1), said second specific immune reaction being directed toward;

(i) said infectious agent;

or

(ii) cells infected with said infectious agent;

or

(iii) uninfected cells;

or

(iv) a combination of any of (2)(i), (2)(ii) and (2)(iii) above.

24. The process according to claim 23, wherein said first specific immune reaction and said second specific immune reaction are directed to at least two different epitopes on said one or more antigens.

25. The process according to claim 23, wherein said first specific immune reaction and said second specific immune reaction are directed to at least two different epitopes on said one or more antigens and are mediated by different components of said subject'"'"'s immune system.

26. The process according to claims 24 or 25, wherein said different components of the first specific immune reaction and the second specific immune reaction are selected from the group consisting of cellular immune reaction elements, humoral immune reaction elements and cytokines.

27. The process, according to claim 26, wherein when said component or components of the specific immune reaction comprise cellular immune response elements, said corresponding component or components of the specific immune reaction comprise humoral immune response elements or cytokines, wherein when said component or components of the specific immune reaction comprise humoral immune response elements, said corresponding component or components of the specific immune reaction comprise cellular immune response elements or cytokines.

28. The process according to claim 26, wherein when said component or components of the specific immune reaction comprise cytokines, said corresponding component or components of the specific immune reaction comprises cellular immune response elements or humoral immune response elements.

29. The process according to claim 23, wherein said one or more antigens are introduced or administered in a single dose or in multiple doses.

30. The process according to claim 23, wherein said one or more antigens are introduced or administered in different dosages.

31. The process according to claim 23, wherein said one or more antigens are introduced or administered in a manner selected from the group consisting of continuous administration and intermittent or periodic administration.

32. The process according to claim 23, wherein said one or more antigens are introduced or administered by a single route or by at least two different routes.

33. The process according to claim 23, wherein said one or more antigens are introduced or administered by a route selected from the group consisting of oral, intravenous, parenteral, transdermal, subcutaneous, intravaginal, intranasal, mucosal, sublingual, aural, intrabronchial, topical, intramuscular, intraperitoneal, rectal, and combinations of any of the foregoing.

34. The process according to claim 23, wherein said one or more antigens are introduced or administered orally.

35. The process according to claim 23, further comprising introducing or administering one or more carriers.

36. The process according to claim 23, wherein said infectious agent comprises a virus.

37. The process according to claim 36, wherein said virus is selected from the group consisting of HBV, HCV, HIV and a combination of any of the foregoing.

38. A process of treating a subject carrying an infectious agent, said process comprising the steps of:

(a) removing immune cells from said subject;

(b) training or adopting said removed cells;

(c) introducing into or administering to said subject said immune cells which have been rendered capable of;

(1) establishing or increasing at least one first specific immune reaction directed against;

(i) said infectious agent;

or

(ii) cells infected with said infectious agent;

or

(iii) a combination of (1)(i) and (1)(ii) above; and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction (a)(1), said second specific immune reaction being directed toward;

(i) said infectious agent;

or

(ii) cells infected with said infectious agent;

or

(iii) uninfected cells;

or

(iv) a combination of any of (2)(i), (2)(ii) and (2)(iii) above;

39. The process according to claim 38, wherein said training or adopting step has been carried out in a surrogate.

40. The process according to claim 38, wherein said training or adopting step has been carried in vitro.

41. A process of treating a subject carrying an infectious agent, said process comprising the steps of:

(a) removing immune cells from a trained donor, or from a naive donor wherein said immune cells have been trained in a surrogate or in vitro;

(b) introducing into or administering to said subject said removed immune cells capable of;

(1) establishing or increasing at least one first specific immune reaction directed against;

(i) said infectious agent;

or

(ii) cells infected with said infectious agent;

or

(iii) a combination of (1)(i) and (1)(ii) above; and

(2) decreasing at least one second specific immune response which is different from said first specific immune reaction (a)(1), said second specific immune response being directed toward;

(i) said infectious agent;

or

(ii) cells infected with said infectious agent;

or

(iii) uninfected cells;

or

(iv) a combination of any of (2)(i), (2)(ii) and (2)(iii) above; and

(c) managing or treating said subject for graft-versus-host complications.

42. The process according to claim 41, wherein said managing or treating step (b) comprises a treatment selected from the group consisting of ablation, administration of immunosuppressive compounds, oral tolerization, and combinations of any of the foregoing.

43. A process of treating a cancerous subject who has a tumor containing cancerous cells, or who has cancerous cells, said process comprising the steps of:

(a) introducing into or administering to said subject one or more specific antigens, said antigen or antigens being capable of;

(1) establishing or increasing at least one first specific immune reaction directed against;

(i) cancer associated antigens;

or

(ii) cancerous cells;

or

(iii) a combination of (1)(i) and (1)(ii); and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction, said second specific immune reaction being directed toward;

(i) said cancer associated antigens;

or

(ii) said cancerous cells;

or

(iii) non-cancerous cells;

or

(iii) a combination of (2)(i), (2)(ii) and (2)(iii).

44. The process according to claim 43, wherein said one or more antigens are introduced or administered in a single dose.

45. The process according to claim 43, wherein said one or more antigens are introduced or administered in multiple doses.

46. The process according to claim 43, wherein said one or more antigens are introduced or administered in different dosages.

47. The process according to claim 43, wherein said one or more antigens comprise antigens having different epitopes.

48. The process according to claim 43, wherein said one or more antigens are introduced or administered continuously.

49. The process according to claim 43, wherein said one or more antigens are introduced or administered intermittently or periodically.

50. The process according to claim 43, wherein said one or more antigens are introduced or administered by a single route.

51. The process according to claim 43, wherein said one or more antigens are introduced or administered by at least two different routes.

52. The process according to claim 43, wherein said one or more antigens are introduced or administered by a route selected from the group consisting of oral, intravenous, parenteral, transdermal, subcutaneous, intravaginal, intranasal, mucosal, sublingual, aural, intrabronchial, topical, intramuscular, intraperitoneal, rectal, and combinations of any of the foregoing.

53. The process according to claim 43, wherein said one or more antigens are introduced or administered orally.

54. The process according to claim 43, further comprising treating said subject with other conventional cancer treatments.

55. A process of treating a cancerous subject who has a tumor containing cancerous cells, or who has cancerous cells, said process comprising the steps of:

(a) removing immune cells from said cancerous subject;

(b) training or adopting said removed cells;

(c) introducing into or administering to said subject said immune cells which have been rendered capable of;

(1) establishing or increasing at least one first specific immune reaction directed against;

(i) cancer associated antigens;

or

(ii) cancerous cells;

or

(iii) a combination of (1)(i) and (1)(ii); and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction (a)(1), said second specific immune reaction being directed toward;

(i) said cancer associated antigens;

or

(ii) said cancerous cells;

or

(iii) non-cancerous cells;

or

(iii) a combination of (2)(i), (2)(ii) and (2)(iii).

56. The process according to claim 55, wherein said training or adopting step has been carried out in a surrogate.

57. The process according to claim 55, wherein said training or adopting step has been carried in vitro.

58. A process of treating a cancerous subject who has a tumor containing cancerous cells, or who has cancerous cells, said process comprising the steps of:

(a) removing immune cells from a trained donor, or from a naive donor wherein said immune cells have been trained in a surrogate or in vitro;

(b) introducing into or administering to said subject said removed immune cells which have been rendered capable of;

(1) establishing or increasing at least one first specific immune reaction directed against;

(i) cancer associated antigens;

or

(ii) cancerous cells;

or

(iii) a combination of (1)(i) and (1)(ii); and

(2) decreasing at least one second specific immune response which is different from said first specific immune reaction (a)(1), said second specific immune response being directed toward;

(i) said cancer associated antigens;

or

(ii) said cancerous cells;

or

(iii) non-cancerous cells;

or

(iii) a combination of (2)(i), (2)(ii) and (2)(iii); and

(c) managing or treating said subject for graft-versus-host complications.

59. The process according to claim 58, wherein said managing or treating step (b) comprises a treatment selected from the group consisting of ablation, administration of immunosuppressive compounds, oral tolerization, and combinations of any of the foregoing.

60. A process for enhancing the immunized state of a subject vaccinated against an infectious agent, said process comprising the steps of:

(a) introducing into or administering to said subject one or more specific antigens, said antigen or antigens being capable of;

(1) establishing or increasing at least one first specific immune reaction directed against said infectious agent; and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction (a)(1), said second specific immune reaction being directed toward;

(i) said infectious agent;

or

(ii) uninfected cells;

or

(iii) a combination of (2)(i) and (2)(ii) above.

61. A process for enhancing the immunized state of a subject vaccinated against an infectious agent, said process comprising the steps of:

(a) removing immune cells from said subject;

(b) training or adopting said removed cells;

(c) introducing into or administering to said subject said immune cells which have been rendered capable of;

(1) establishing or increasing at least one first specific immune reaction directed against said infectious agent; and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction (a)(1), said second specific immune reaction being directed toward;

(i) said infectious agent;

or

(ii) uninfected cells;

or

(iii) a combination of (2)(i) and (2)(ii) above.

62. The process according to claim 61, wherein said training or adopting step has been carried out in a surrogate.

63. The process according to claim 61, wherein said training or adopting step has been carried out in vitro.

64. A process for enhancing the immunized state of a subject vaccinated against an infectious agent, said process comprising the steps of:

(a) removing immune cells from a trained donor, or from a naive donor wherein said immune cells have been trained in a surrogate or in vitro;

(b) introducing into or administering to said subject said removed immune cells which have been rendered capable of;

(1) establishing or increasing at least one first specific immune reaction directed against said infectious agent; and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction (a)(1), said second specific immune reaction being directed toward;

(i) said infectious agent;

or

(ii) uninfected cells;

or

(iii) a combination of (2)(i) and (2)(ii) above; and

(c) managing or treating said subject for graft-versus-host complications.

65. The process according to claim 64, wherein said managing or treating step (b) comprises a treatment selected from the group consisting of ablation, administration of immunosuppressive compounds, oral tolerization, and combinations of any of the foregoing.

66. A process for vaccinating a subject against an infectious agent, said process comprising the steps of:

(a) introducing into or administering to said subject one or more first antigens capable of establishing an immune response against said infectious agent; and

(b) introducing into or administering to said subject one or more second specific antigens capable of;

(1) establishing or increasing at least one first specific immune reaction directed against said infectious agent; and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction (a)(1), said second specific immune reaction being directed toward;

(i) said infectious agent;

or

(ii) uninfected cells;

or

(iii) a combination of (2)(i) and (2)(ii) above;

67. The process according to claim 66, wherein said first antigens and said second specific antigens are different antigens or contain different epitopes.

68. The process according to claim 66, wherein said first antigens and said second specific antigens are introduced or administered by different regimens, dosages or routes.

69. A process for vaccinating a subject against an infectious agent, said process comprising the steps of:

(a) introducing into or administering to said subject one or more first antigens capable of establishing an immune response against said infectious agent; and

(b) introducing into or administering to said subject immune cells capable of;

(1) establishing or increasing at least one first specific immune reaction directed against said infectious agent; and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction (a)(1), said second specific immune reaction being directed toward;

(i) said infectious agent;

or

(ii) uninfected cells;

or

(iii) a combination of (2)(i) and (2)(ii) above;

wherein said immune cells have been removed from said subject and trained or adopted prior to said introducing or administering step (b).

70. A process for vaccinating a subject against an infectious agent, said process comprising the steps of:

(a) introducing into or administering to said subject one or more first antigens capable of establishing an immune response against said infectious agent;

(b) introducing into or administering to said subject immune cells capable of;

(1) establishing or increasing at least one first specific immune reaction directed against said infectious agent; and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction (a)(1), said second specific immune reaction being directed toward;

(i) said infectious agent;

or

(ii) uninfected cells;

or

(iii) a combination of (2)(i) and (2)(ii) above;

wherein prior to said introducing or administering step (b), said immune cells have been removed from a trained donor, or from a naive donor wherein said immune cells were trained in a surrogate or in vitro; and

(c) managing or treating said subject for graft-versus-host complications.

71. The process according to claim 70, wherein said managing or treating step (b) comprises a treatment selected from the group consisting of ablation, administration of immunosuppressive compounds, oral tolerization, and combinations of any of the foregoing.

72. A therapeutic composition of matter comprising specific antigens capable of:

(1) establishing or increasing at least one first specific immune reaction directed against an infectious agent of interest, cells infected with said infectious agent, or both, and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction, said second specific immune reaction being directed toward said infectious agent, cells infected with said infectious agent, uninfected cells, or a combination of any of said infectious agent, said infected cells and said uninfected cells.

73. A therapeutic composition of matter comprising trained or adopted immune cells capable of:

(1) establishing or increasing at least one first specific immune reaction directed against an infectious agent of interest, cells infected with said infectious agent, or both, and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction, said second specific immune reaction being directed toward said infectious agent, cells infected with said infectious agent, uninfected cells, or a combination of any of said infectious agent, said infected cells and said uninfected cells.

74. A therapeutic composition of matter comprising trained or adopted immune cells capable of:

(1) establishing or increasing at least one first specific immune reaction directed against cancer associated antigens, cancerous cells, or a combination of said cancer associated antigens and said cancerous cells; and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction, said second specific immune reaction being directed toward said cancer associated antigens;

said cancerous cells;

non-cancerous cells;

or a combination of said cancer associated antigens, said cancerous cells and said non-cancerous cells.

75. A therapeutic composition of matter comprising trained or adopted immune cells capable of:

(1) establishing or increasing at least one first specific immune reaction directed against cancer associated antigens;

cancerous cells;

or a combination of said cancer associated antigens and said cancerous cells; and

(2) decreasing at least one second specific immune reaction which is different from said first specific immune reaction (1), said second specific immune reaction being directed toward said cancer associated antigens;

said cancerous cells, non-cancerous cells, and a combination of said cancer associated antigens, said cancerous cells and said non-cancerous cells.