Methods of and compositions for inhibiting the proliferation of mammalian cells

• US 20050113327A1
• Filed: 09/29/2004
• Published: 05/26/2005
• Est. Priority Date: 08/30/1999
• Status: Active Grant

• Current Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Original Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Inventors: Schwartz, Betty, Smirnoff, Patricia, Shoseyov, Oded, Roiz, Levava
• Granted Patent: US 7,811,981 B2
• Time in Patent Office: Days
• US Class Current: 514/44.R
• 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 38/465 acting on ester bonds (3.1), e.g. lipases, ribonucleases
• 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
• CPC Class Codes: C12N 9/22 Ribonucleases RNAses, DNAses catalytic nucleic acids C12N15/113
• CPC Class Codes: C12Y 301/27001 Ribonuclease T2 (3.1.27.1)
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A method of preventing, inhibiting and/or reversing cell motility, actin filament assembly or disassembly, proliferation, colonization, differentiation, accumulation and/or development of abnormal cells in a subject is disclosed. The method is effected by administering to the subject a therapeutically effective amount of a ribonuclease of the T2 family having actin binding activity.

Claims

1. A method of preventing, inhibiting and/or reversing proliferation, colonization, differentiation and/or development of abnormally proliferating cells in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polynucleotide encoding and capable of expressing in vivo a recombinant ribonuclease of the T2 family having an actin binding activity.

2. The method of claim 1, wherein said ribonuclease of the T2 family substantially lacks ribonucleolytic activity.

3. The method of claim 1, wherein the abnormally proliferating cells are cancerous cells.

4. The method of claim 1, wherein the abnormally proliferating cells are cells associated with a proliferative disorder or disease selected from the group consisting of papilloma, blastoglioma, Kaposi'"'"'s sarcoma, melanoma, lung cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, astrocytoma, head cancer, neck cancer, bladder cancer, breast cancer, lung cancer, colorectal cancer, thyroid cancer, pancreatic cancer, gastric cancer, hepatocellular carcinoma, leukemia, lymphoma, Hodgkin'"'"'s disease, Burkitt'"'"'s disease, arthritis, rheumatoid arthritis, diabetic retinopathy, angiogenesis, restenosis, in-stent restenosis and vascular graft restenosis, proliferative vitreoretinopathy, chronic inflammatory proliferative disease, dermatofibroma and psoriasis.

5. The method of claim 1, wherein said step of administering to the subject said therapeutically effective amount of a polynucleotide encoding and capable of expressing in vivo said recombinant ribonuclease of the T2 family is effected by an administration mode selected from the group consisting of oral administration, topical administration, transmucosal administration, parenteral administration and by inhalation.

6. The method of claim 1, wherein said ribonuclease of the T2 family is RNase B1.

7. The method of claim 1, wherein said ribonuclease of the T2 family is selected from the group consisting of RNase T2, RNase Rh, RNase M, RNase Trv, RNase Irp, RNase Le2, RNase Phyb, RNase LE, RNase MC, RNase CL1, RNase Bsp1, RNase RCL2, RNase Dm, RNase Oy and RNase Tp.

8. A pharmaceutical composition comprising, as an active ingredient, a ribonuclease of the T2 family having an actin binding activity, and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8, wherein the abnormally proliferating cells are cancerous cells.

10. The pharmaceutical composition of claim 8, wherein the abnormally proliferating cells are cells associated with a proliferative disorder or disease selected from the group consisting of papilloma, blastoglioma, Kaposi'"'"'s sarcoma, melanoma, lung cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, astrocytoma, head cancer, neck cancer, bladder cancer, breast cancer, lung cancer, colorectal cancer, thyroid cancer, pancreatic cancer, gastric cancer, hepatocellular carcinoma, leukemia, lymphoma, Hodgkin'"'"'s disease, Burkitt'"'"'s disease, arthritis, rheumatoid arthritis, diabetic retinopathy, angiogenesis, restenosis, in-stent restenosis and vascular graft restenosis, proliferative vitreoretinopathy, chronic inflammatory proliferative disease, dermatofibroma and psoriasis.

11. The pharmaceutical composition of claim 8, wherein said ribonuclease of the T2 family having an actin binding activity is selected from the group consisting of RNase T2, RNase Rh, RNase M, RNase Trv, RNase Irp, RNase Le2, RNase Phyb, RNase LE, RNase MC, RNase CL1, RNase Bsp1, RNase RCL2, RNase Dm, RNase Oy and RNase Tp.

12. A pharmaceutical composition comprising, as an active ingredient, a polynucleotide encoding and capable of expressing in vivo a recombinant ribonuclease of the T2 family having an actin binding activity, and a pharmaceutically acceptable carrier.

13. The pharmaceutical composition of claim 12, wherein said ribonuclease of the T2 family substantially lacks ribonucleolytic activity.

14. The pharmaceutical composition of claim 12, wherein the abnormally proliferating cells are cancerous cells.

15. The pharmaceutical composition of claim 12, wherein the abnormally proliferating cells are cells associated with a proliferative disorder or disease selected from the group consisting of papilloma, blastoglioma, Kaposi'"'"'s sarcoma, melanoma, lung cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, astrocytoma, head cancer, neck cancer, bladder cancer, breast cancer, lung cancer, colorectal cancer, thyroid cancer, pancreatic cancer, gastric cancer, hepatocellular carcinoma, leukemia, lymphoma, Hodgkin'"'"'s disease, Burkitt'"'"'s disease, arthritis, rheumatoid arthritis, diabetic retinopathy, angiogenesis, restenosis, in-stent restenosis and vascular graft restenosis, proliferative vitreoretinopathy, chronic inflammatory proliferative disease, dermatofibroma and psoriasis.

16. The pharmaceutical composition of claim 12, wherein said ribonuclease of the T2 family is RNase B1.

17. The pharmaceutical composition of claim 12, wherein said ribonuclease of the T2 family is selected from the group consisting of RNase T2, RNase Rh, RNase M, RNase Trv, RNase Irp, RNase Le2, RNase Phyb, RNase LE, RNase MC, RNase CL1, RNase Bsp1, RNase RCL2, RNase Dm, RNase Oy and RNase Tp.

18. A method of preparing a medicament useful in preventing, inhibiting and/or reversing proliferation, colonization, differentiation and/or development of abnormally proliferating cells comprising combining a ribonuclease of the T2 family having an actin binding activity with a pharmaceutically acceptable carrier.

19. The method of claim 18, wherein said ribonuclease of the T2 family substantially lacks ribonucleolytic activity.

20. The method of claim 18, further comprising inactivating the ribonucleolytic activity of said ribonuclease of the T2 family.

21. The method of claim 20, wherein said step of inactivating the ribonucleolytic activity of said ribonuclease of the T2 family is effected by a process selected from the group consisting of autoclaving and chemically denaturing.

22. The method of claim 18, further comprising identifying the medicament as a treatment for a specified cancer.

23. The method of claim 18, further comprising identifying the medicament as a treatment for a specified proliferative disorder or disease.

24. The method of claim 23, wherein the specified proliferative disorder or disease is selected from the group consisting of papilloma, blastoglioma, Kaposi'"'"'s sarcoma, melanoma, lung cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, astrocytoma, head cancer, neck cancer, bladder cancer, breast cancer, lung cancer, colorectal cancer, thyroid cancer, pancreatic cancer, gastric cancer, hepatocellular carcinoma, leukemia, lymphoma, Hodgkin'"'"'s disease, Burkitt'"'"'s disease, arthritis, rheumatoid arthritis, diabetic retinopathy, angiogenesis, restenosis, in-stent restenosis and vascular graft restenosis proliferative vitreoretinopathy, chronic inflammatory proliferative disease, dermatofibroma and psoriasis.

25. The method of claim 18, wherein said ribonuclease of the T2 family is RNase B1.

26. The method of claim 18, wherein said ribonuclease of the T2 family is selected from the group consisting of RNase T2, RNase Rh, RNase M, RNase Trv, RNase Irp, RNase Le2, RNase Phyb, RNase LE, RNase MC, RNase CL1, RNase Bsp1, RNase RCL2, RNase Dm, RNase Oy and RNase Tp.

27. A method of preparing a medicament useful in preventing, inhibiting and/or reversing proliferation, colonization, differentiation and/or development of abnormally proliferating cells comprising combining a polynucleotide encoding and capable of expressing in vivo a recombinant ribonuclease of the T2 family having an actin binding activity with a pharmaceutically acceptable carrier.

28. The method of claim 27, wherein said ribonuclease of the T2 family substantially lacks ribonucleolytic activity.

29. The method of claim 27, further comprising inactivating the ribonucleolytic activity of said ribonuclease of the T2 family.

30. The method of claim 29, wherein said step of inactivating the ribonucleolytic activity of said ribonuclease of the T2 family is effected by a process selected from the group consisting of autoclaving and chemically denaturing.

31. The method of claim 27, further comprising identifying the medicament as a treatment for a specified cancer.

32. The method of claim 27, further comprising identifying the medicament as a treatment for a specified proliferative disorder or disease.

33. The method of claim 32, wherein the specified proliferative disorder or disease is selected from the group consisting of papilloma, blastoglioma, Kaposi'"'"'s sarcoma, melanoma, lung cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, astrocytoma, head cancer, neck cancer, bladder cancer, breast cancer, lung cancer, colorectal cancer, thyroid cancer, pancreatic cancer, gastric cancer, hepatocellular carcinoma, leukemia, lymphoma, Hodgkin'"'"'s disease, Burkitt'"'"'s disease, arthritis, rheumatoid arthritis, diabetic retinopathy, angiogenesis, restenosis, in-stent restenosis and vascular graft restenosis, proliferative vitreoretinopathy, chronic inflammatory proliferative disease, dermatofibroma and psoriasis.

34. The method of claim 27, wherein said ribonuclease of the T2 family is RNase B1.

35. The method of claim 27, wherein said ribonuclease of the T2 family is selected from the group consisting of RNase T2, RNase Rh, RNase M, RNase Trv, RNase Irp, RNase Le2, RNase Phyb, RNase LE, RNase MC, RNase CL1, RNase Bsp1, RNase RCL2, RNase Dm, RNase Oy and RNase Tp.

36. A method of treating a tumor in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polynucleotide encoding and capable of expressing in vivo a recombinant ribonuclease of the T2 family having an actin binding activity.

37. A method of preventing, inhibiting and/or reversing the development a tumor in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polynucleotide encoding and capable of expressing in vivo a recombinant ribonuclease of the T2 family having an actin binding activity.

38. A method of preventing, inhibiting and/or reversing transformation of a benign tumor to a malignant tumor in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polynucleotide encoding and capable of expressing in vivo a recombinant ribonuclease of the T2 family having an actin binding activity.

39. A method of preventing, inhibiting and/or reversing tumor angiogenesis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polynucleotide encoding and capable of expressing in vivo a recombinant ribonuclease of the T2 family having an actin binding activity.

40. A method of reducing the number of individual tumors in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polynucleotide encoding and capable of expressing in vivo a recombinant ribonuclease of the T2 family having an actin binding activity.

41. A method of reducing tumor size in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polynucleotide encoding and capable of expressing in vivo a recombinant ribonuclease of the T2 family having an actin binding activity.

42. A method of reducing a number of malignant tumors in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polynucleotide encoding and capable of expressing in vivo a recombinant ribonuclease of the T2 family having an actin binding activity.

43. A method of preventing, inhibiting and/or reversing transformation of a tissue into a tumor in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polynucleotide encoding and capable of expressing in vivo a recombinant ribonuclease of the T2 family having an actin binding activity.

44. A method of treating and/or preventing a disease or condition characterized by excessive cell motility in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

45. The method of claim 44, wherein said ribonuclease of the T2 family is a recombinant protein, expressed in a heterologous expression system.

46. The method of claim 45, wherein said heterologous expression system is selected from the group consisting of bacterial expression system, yeast expression system and higher cell expression system.

47. The method of claim 44, wherein a ribonuclease activity of said ribonuclease protein is thermostable.

48. The method of claim 44, wherein said ribonuclease of the T2 family is substantially devoid of ribonuclease activity.

49. The method of claim 48, wherein a ribonuclease activity of said ribonuclease protein is thermostable.

50. The method of claim 49, wherein an actin binding activity of said ribonuclease protein is thermostable.

51. The method of claim 44, wherein said ribonuclease of the T2 family having actin binding activity is selected from the group consisting of RNase T2, RNase Rh, RNase M, RNase Trv, RNase Irp, RNase Le2, RNase Phyb, RNase LE, RNase MC, RNase CL1, RNase Bsp1, RNase RCL2, RNase Dm, RNase Oy and RNase Tp.

52. The method of claim 44, wherein said expressible polynucleotide is selected capable of stable integration into a genome of a cell of said subject.

53. The method of claim 44, wherein said disease or condition characterized by excessive cellular motility is selected from the group consisting of an inflammatory disease, a neurodegenerative disease and a cancer.

54. The method of claim 44, wherein said disease or condition characterized by excessive cellular motility is a cancer.

55. The method of claim 44, wherein administering to the subject said therapeutically effective amount of said ribonuclease of the T2 family or said expressible polynucleotide encoding said ribonuclease is effected by an administration mode selected from the group consisting of oral administration, intravenous administration, subcutaneous administration, systemic administration, topical administration, transmucosal administration, parenteral administration, rectal administration and inhalation.

56. A method of inhibiting motility of a cell, the method comprising providing to the cell a ribonuclease of the T2 family having an actin binding activity or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family, thereby inhibiting motility of said cell.

57. The method of claim 56, wherein said ribonuclease of the T2 family is a recombinant protein, expressed in a heterologous expression system.

58. The method of claim 57, wherein said heterologous expression system is selected from the group consisting of bacterial expression system, yeast expression system and higher cell expression system.

59. The method of claim 56, wherein a ribonuclease activity of said ribonuclease of the T2 family is thermostable.

60. The method of claim 56, wherein said ribonuclease of the T2 family is substantially devoid of ribonuclease activity.

61. The method of claim 56, wherein a ribonuclease activity of said ribonuclease of the T2 family is thermostable.

62. The method of claim 61, wherein an actin binding activity of said ribonuclease protein is thermostable.

63. The method of claim 56, wherein said ribonuclease of the T2 family having actin binding activity is selected from the group consisting of RNase T2, RNase Rh, RNase M, RNase Trv, RNase Irp, RNase Le2, RNase Phyb, RNase LE, RNase MC, RNase CL1, RNase Bsp1, RNase RCL2, RNase Dm, RNase Oy and RNase Tp.

64. The method of claim 56, wherein said expressible polynucleotide is selected capable of stable integration into a genome of the cell.

65. The method of claim 56, wherein said cell is a cancer cell.

66. The method of claim 56, wherein said providing is effected in vitro or in vivo.

67. A method of treating and/or preventing a disease or condition characterized by abnormal accumulation of cells in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

68. The method of claim 67, wherein said ribonuclease of the T2 family is a recombinant protein, expressed in a heterologous expression system.

69. The method of claim 68, wherein said heterologous expression system is selected from the group consisting of bacterial expression system, yeast expression system and higher cell expression system.

70. The method of claim 67, wherein said ribonuclease of the T2 family is substantially devoid of ribonuclease activity.

71. The method of claim 67, wherein said ribonuclease of the T2 family having actin binding activity is selected from the group consisting of RNase T2, RNase Rh, RNase M, RNase Trv, RNase Irp, RNase Le2, RNase Phyb, RNase LE, RNase MC, RNase CL1, RNase Bsp1, RNase RCL2, RNase Dm, RNase Oy and RNase Tp.

72. The method of claim 67, wherein said disease or condition characterized by abnormal cellular accumulation is selected from the group consisting of an inflammatory disease, a neurodegenerative disease and a cancer.

73. A method of inhibiting actin filament assembly and disassembly in a cell, the method comprising providing t) the cell a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family, thereby inhibiting actin filament assembly or disassembly of said cell.

74. The method of claim 73, wherein said ribonuclease of the T2 family is a recombinant protein, expressed in a heterologous expression system.

75. The method of claim 74, wherein said heterologous expression system is selected from the group consisting of bacterial expression system, yeast expression system and higher cell expression system.

76. The method of claim 73, wherein said ribonuclease of the T2 family is substantially devoid of ribonuclease activity.

77. The method of claim 73, wherein said ribonuclease of the T2 family having actin binding activity is selected from the group consisting of RNase T2, RNase Rh, RNase M, RNase Trv, RNase Irp, RNase Le2, RNase Phyb, RNase LE, RNase MC, RNase CL1, RNase Bsp1, RNase RCL2, RNase Dm, RNase Oy and RNase Tp.

78. The method of claim 73, wherein said expressible polynucleotide is selected capable of stable integration into a genome of the cell.

79. The method of claim 73, wherein said cell is a cancer cell.

80. The method of claim 73, wherein said providing is effected in vitro or in vivo.

81. A method of enhancing apoptosis of a cell, the method comprising providing to the cell an effective concentration of a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family, thereby enhancing apoptosis.

82. The method of claim 81, wherein said ribonuclease of the T2 family is a recombinant protein, expressed in a heterologous expression system.

83. The method of claim 82, wherein said heterologous expression system is selected from the group consisting of bacterial expression system, yeast expression system and higher cell expression system.

84. The method of claim 81, wherein said ribonuclease of the T2 family is substantially devoid of ribonuclease activity.

85. The method of claim 81, wherein said ribonuclease of the T2 family having actin binding activity is selected from the group consisting of RNase T2, RNase Rh, RNase M, RNase Trv, RNase Irp, RNase Le2, RNase Phyb, RNase LE, RNase MC, RNase CL1, RNase Bsp1, RNase RCL2, RNase Dm, RNase Oy and RNase Tp.

86. The method of claim 81, wherein said expressible polynucleotide is selected capable of stable integration into a genome of the cell.

87. The method of claim 81, wherein said cell is a cancer cell.

88. The method of claim 81, wherein said providing is effected in vitro or in vivo.

89. A method of isolating a thermostable ribonuclease of the T2 family, the method comprising:

heat denaturating a sample which comprises cells expressing a ribonuclease of the T2 family so as to obtain a heat denatured sample;

isolating a supernatant of said heat denatured sample; and

identifying a fraction of said supernatant having a thermostable ribonuclease of the T2 family; and

purifying said fraction having said thermostable ribonuclease of the T2 family from said supernatant to substantial purity.

90. The method of claim 89, wherein said heat denaturing is effected by a temperature of at least 90°

C.

91. The method of claim 90, wherein said heat denaturing is performed for at least 10 minutes.

92. The method of claim 89, wherein said identifying said fraction is effected by monitoring ribonucleolytic actvity.

93. The method of claim 89, wherein said purifying said fraction is effected by column chromatography.

94. A method of inactivating a ribonuclease activity, yet maintaining an actin binding activity of a ribonuclease of the T2 family, the method comprising subjecting said ribonuclease to denaturing conditions sufficient for substantially inactivating said ribonuclease activity, yet maintaining said actin binding activity.

95. The method of claim 94, wherein said inactivating said ribonuclease activity is effected by a process selected from the group consisting of autoclaving and chemical denaturation.

96. The method of claim 94, wherein said ribonuclease is a recombinant ribonuclease.

97. An isolated ribonuclease of the T2 family being substantially devoid of ribonuclease activity and having an actin binding activity.

98. A method of preparing a medicament useful in treating and/or preventing a disease or condition characterized by excessive cell motility comprising combining a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family having actin binding activity, with a pharmaceutically acceptable carrier.

99. The method of claim 98, wherein said ribonuclease of the T2 family is a recombinant protein, expressed in a heterologous expression system.

100. The method of claim 99, wherein said heterologous expression system is selected from the group consisting of bacterial expression system, yeast expression system and higher cell expression system.

101. The method of claim 98, wherein said ribonuclease of the T2 family is substantially devoid of ribonuclease activity.

102. The method of claim 98, wherein said ribonuclease of the T2 family having actin binding activity is selected from the group consisting of RNase T2, RNase Rh, RNase M, RNase Trv, RNase Irp, RNase Le2, RNase Phyb, RNase LE, RNase MC, RNase CL1, RNase Bsp1, RNase RCL2, RNase Dm, RNase Oy and RNase Tp.

103. A method of preparing a medicament useful in treating and/or preventing a disease or condition characterized by abnormal accumulation of cells comprising combining a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family, with a pharmaceutically acceptable carrier.

104. The method of claim 103, wherein said ribonuclease of the T2 family is a recombinant protein, expressed in a heterologous expression system.

105. The method of claim 104, wherein said heterologous expression system is selected from the group consisting of bacterial expression system, yeast expression system and higher cell expression system.

106. The method of claim 103, wherein said ribonuclease of the T2 family is substantially devoid of ribonuclease activity.

107. The method of claim 103, wherein said ribonuclease of the T2 family having actin binding activity is selected from the group consisting of RNase T2, RNase Rh, RNase M, RNase Trv, RNase Irp, RNase Le2, RNase Phyb, RNase LE, RNase MC, RNase CL1, RNase Bsp1, RNase RCL2, RNase Dm, RNase Oy and RNase Tp.

108. A method of enhancing chemotherapeutic treatment of a cancer comprising administering to a subject in need thereof, in combination with said chemotherapeutic treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

109. A method of enhancing radiotherapy treatment of a cancer comprising administering to a subject in need thereof, in combination with said radiotherapy treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

110. A method of enhancing phototherapy treatment of a cancer comprising administrating to a subject in need thereof, in combination with said phototherapy treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

111. A method of enhancing photodynamic therapy treatment of a cancer comprising administering to a subject in need thereof, in combination with said photodynamic therapy treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

112. A method of enhancing surgical treatment of a cancer comprising administering to a subject in need thereof, in combination with said surgical treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

113. A method of enhancing nutritional treatment of a cancer comprising administering to a subject in need thereof, in combination with said nutritional treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

114. A method of enhancing ablative therapy treatment of a cancer comprising administering to a subject in need thereof, in combination with said ablative therapy treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

115. A method of enhancing combined radiotherapy and chemotherapy treatment of a cancer comprising administering to a subject in need thereof, in combination with said combined radiotherapy and chemotherapy treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

116. A method of enhancing brachiotherapy treatment of a cancer comprising administering to a subject in need thereof, in combination with said brachiotherapy treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

117. A method of enhancing proton beam therapy treatment of a cancer comprising administering to a subject in need thereof, in combination with said proton beam therapy treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

118. A method of enhancing immunotherapy treatment of a cancer comprising administering to a subject in need thereof, in combination with said immunotherapy treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

119. A method of enhancing cellular therapy treatment of a cancer comprising administering to a subject in need thereof, in combination with said cellular therapy treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.

120. A method of enhancing photon beam radiosurgical therapy treatment of a cancer comprising administering to a subject in need thereof, in combination with said photon beam radiosurgical therapy treatment, a ribonuclease of the T2 family having an actin binding activity, or a polynucleotide encoding and capable of expressing in vivo said ribonuclease of the T2 family.