Human papillomavirus, varicella-zoster virus, and rabies virus antigens and uses thereof in cancer immunotherapy
Patent Information
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES
- Filing Date
- 2026-05-27
- Publication Date
- 2026-07-10
Smart Images
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Abstract
Description
Abstract This article provides antigens for varicella-zoster virus vaccines, human papillomavirus vaccines, and rabies virus vaccines, their compositions, and their use in cancer immunotherapy and cancer treatment.
Claims
060734-783069 CLAIMS What is claimed is:
1. A method of treating a cancer in a subject in need thereof, comprising administering to the subject a composition comprising one or more varicella-zoster virus (VZV) antigens from a VZV glycoprotein E (gE) protein, wherein the subject has been previously immunized against VZV, and wherein the composition is administered at the site of the cancer.
2. The method of claim 1, wherein the cancer is a solid tumor.
3. The method of claim 2, wherein the composition is administered via intratumoral or peritumoral injection.
4. The method of claim 1, wherein the VZV antigens comprise a truncated VZV gE protein.
5. The method of claim 4, wherein the truncated VZV gE protein comprises the amino acid sequence set forth in SEQ ID NO:
2.
6. The method of claim 1, wherein the VZV antigens comprise one or more MHC-I- or MHC-II-restricted peptides from VZV gE.
7. The method of claim 6, wherein the amino acid sequence of the VZV gE is set forth in SEQ ID NO:
1.
8. The method of claim 7, wherein the VZV antigens comprise one or more MHC- II-restricted VZV gE peptides, and wherein each VZV gE peptide independently comprises the amino acid sequence set forth in one of SEQ ID NOs: 3-156. 93155272.1 35060734-783069 9. The method of claim 1, wherein the composition comprises or is administered in combination with an adjuvant.
10. The method of claim 9, wherein the adjuvant comprises one or more of poly(I:C), poly-ICLC, a 3-O-desacyl-4’-monophosphoryl lipid A (MPL), QS-21, aluminum hydroxide, and aluminum hydroxyphosphate.
11. The method of claim 10, wherein the adjuvant comprises MPL and QS-21.
12. The method of claim 11, wherein the adjuvant is AS01B.
13. The method of claim 12, wherein the VZV antigen comprises the truncated VZV gE polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
2.
14. The method of claim 13, wherein the VZV antigen and the adjuvant are contained in SHINGRIX.
15. The method of claim 10, wherein the adjuvant comprises poly(I:C), wherein the VZV antigens comprise one or more VZV gE peptides, and wherein each VZV gE peptide independently comprises the amino acid sequence set forth in one of SEQ ID NOs: 3-156.
16. The method of claim 1, wherein the composition is administered 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 times, wherein each administration is performed every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 weeks.
17. The method of claim 16, wherein the cancer is a solid tumor, wherein the composition is administered as one or more series of injections each consisting of 6 injections, and wherein the series of injections is repeated until the solid tumor shrinks or disappears. 93155272.1 36060734-783069 18. A method of treating a cancer in a subject in need thereof, comprising administering to the subject a composition comprising one or more human papillomavirus (HPV) antigens from an HPV L1 polypeptide, wherein the subject has been previously immunized against HPV, and wherein the composition is administered at the site of the cancer.
19. The method of claim 18, wherein the cancer is a tumor.
20. The method of claim 19, wherein the composition is administered via intratumoral or peritumoral injection.
21. The method of claim 18, wherein the HPV is type 16 (HPV16) or 18 (HPV18).
22. The method of claim 21, wherein the HPV antigens comprise one or more MHC- I- or MHC-II-restricted peptides of the HPV L1 polypeptide.
23. The method of claim 22, wherein the HPV antigens comprise one or more MHC- II-restricted HPV L1 peptides, and wherein each HPV L1 peptide independently comprises an HPV16 peptide comprising the amino acid sequence set forth in one of SEQ ID NOs: 1390-1513 or an HPV18 peptide comprising the amino acid sequence set forth in one of SEQ ID NOs: 1514-1637.
24. The method of claim 22, wherein the HPV antigens comprise one or more MHC- I-restricted HPV L1 peptides, and wherein each HPV L1 peptide independently comprises a HPV16 peptide comprising the amino acid sequence set forth in one of SEQ ID NOs: 1638-2632 or 3632-3645 or a HPV18 peptide comprising the amino acid sequence set forth in one of SEQ ID NOs: 2633-3631 or 3646-3651. 93155272.1 37060734-783069 25. The method of claim 24, wherein the HPV antigens comprise the MHC-I- restricted HPV16 L1 peptide comprising the amino acid sequence set forth in SEQ ID NO: 1776.
26. The method of claim 18-24, wherein the composition comprises or is administered in combination with an adjuvant.
27. The method of claim 26, wherein the adjuvant comprises one or more of poly(I:C), poly-ICLC, a 3-O-desacyl-4’-monophosphoryl lipid A (MPL), QS-21, aluminum hydroxide, and aluminum hydroxyphosphate.
28. The method of claim 27, wherein the adjuvant comprises poly(I:C).
29. The method of claim 27, wherein the adjuvant comprises MPL.
30. The method of claim 29, wherein the adjuvant further comprises QS21.
31. The method of claim 30, wherein the composition comprises the truncated VZV gE protein comprising the amino acid sequence set forth in SEQ ID NO:
2.
32. The method of claim 31, wherein the composition is SHINGRIX.
33. The method of claim 29, wherein the adjuvant further comprises aluminum hydroxyphosphate.
34. The method of claim 33, wherein the adjuvant is AS04.
35. The method of claim 18, wherein the composition is administered 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 times, wherein each administration is performed every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 weeks. 93155272.1 38060734-783069 36. The method of claim any one of claims 1-35, wherein the cancer is a solid tumor, and wherein the dose of the one or more antigens is determined relative to tumor volume.
37. The method of claim 36, wherein the dose is at least 1 μg / cm3.
38. The method of claim any one of claims 1-37, wherein the one or more antigens are administered in two or more escalating doses.
39. The method of claim 38, wherein the dose of the one or more antigens is determined individually for the subject.
40. The method of claim 38 or 39, wherein the starting dose of the one or more antigens is determined by an immune assay on autologous peripheral blood mononuclear cells.
41. The method of claim 38 or 39, wherein the starting dose of the one or more antigens is determined by a delayed-type hypersensitivity skin test.
42. The method of claim of claim 38, wherein each subsequent dose after an immediately preceding dose is escalated until an objective is achieved in the subject, wherein the objective is selected from the group consisting of: an objective clinical response in the subject, shrinkage of the cancer, and a substantial toxicity in the subject.
43. The method of claim 42, wherein after the objective is achieved, a subsequent dose of the antigens or peptides is maintained or decreased relative to a preceding dose; or no additional composition is administered to the subject.
44. A method of treating a cancer in a subject in need thereof, comprising administering to the subject a composition comprising one or more tumor-associated antigens 93155272.1 39060734-783069 and one or more varicella-zoster virus (VZV) antigens from a VZV glycoprotein E (gE) protein, wherein the subject has been previously immunized against VZV, and wherein the composition is administered at the site of the cancer.
45. The method of claim 44, wherein the composition further comprises one or more human papillomavirus (HPV) antigens from an HPV L1 polypeptide, and wherein the subject has further been previously vaccinated against HPV.
46. The method of claim 44, wherein the cancer is a tumor.
47. The method of claim 44, wherein the composition is administered via intratumoral or peritumoral injection.
48. The method of claim 45, wherein the HPV is type 16 (HPV16) or 18 (HPV18).
49. The method of claim 48, wherein the HPV antigens comprise one or more MHC- I- or MHC-II-restricted peptides of the HPV L1 polypeptide.
50. The method of claim 49, wherein the HPV antigens comprise one or more MHC- II-restricted HPV L1 peptides, and wherein each HPV L1 peptide independently comprises an HPV16 peptide comprising the amino acid sequence set forth in one of SEQ ID NOs: 1390-1513 or an HPV18 peptide comprising the amino acid sequence set forth in one of SEQ ID NOs: 1514-1637.
51. The method of claim 49, wherein the HPV antigens comprise one or more MHC- I-restricted HPV L1 peptides, and wherein each HPV L1 peptide independently comprises a HPV16 peptide comprising the amino acid sequence set forth in one of SEQ ID NOs: 1638-2632 93155272.1 40060734-783069 or 3632-3645 or a HPV18 peptide comprising the amino acid sequence set forth in one of SEQ ID NOs: 2633-3631 or 3646-3651.
52. The method of claim 51, wherein the HPV antigens comprise the MHC-I- restricted HPV16 L1 peptide comprising the amino acid sequence set forth in SEQ ID NO: 1776.
53. The method of claim 44, wherein the VZV antigens comprise a truncated VZV gE protein.
54. The method of claim 53, wherein the truncated VZV gE protein comprises the amino acid sequence set forth in SEQ ID NO:
2.
55. The method of claim 44, wherein the VZV antigens comprise one or more MHC- I- or MHC-II-restricted peptides from VZV gE.
56. The method of claim 55, wherein the amino acid sequence of the VZV gE is set forth in SEQ ID NO:
1.
57. The method of claim 56, wherein the VZV antigens comprise one or more MHC- II-restricted VZV gE peptides, and wherein each VZV gE peptide independently comprises the amino acid sequence set forth in one of SEQ ID NOs: 3-156.
58. The method of claim 48, wherein the subject is human leukocyte antigen (HLA)- A0201 (HLA-A0201)-positive; wherein the cancer comprises a tumor that does not express E6 or E7 oncoproteins from HPV16 and HPV18; and wherein the composition comprises a truncated VZV gE protein, an HPV16 L1 peptide comprising the sequence set forth in SEQ ID NO: 1960, and an HPV18 L1 peptide comprising the sequence set forth in SEQ ID NO: 3649. 93155272.1 41060734-783069 59. The method of claim 44, wherein the tumor expresses at least one of the tumor- associated antigens.
60. The method of claim 59, wherein the subject is human leukocyte antigen (HLA)- A0201 (HLA-A0201)-positive; wherein the cancer comprises a tumor that expresses one or more of E6 and E7 oncoproteins from one of HPV16 and HPV18; and wherein the composition comprises: a truncated VZV gE protein; an HPV16 L1 peptide comprising the sequence set forth in SEQ ID NO: 1960; an HPV18 L1 peptide comprising the sequence set forth in SEQ ID NO: 3649; HPV16 E7 peptides comprising the sequences set forth in SEQ ID NOs: 5235, 3896, and 5236, wherein each HPV16 E7 peptide comprises one of the sequences; and HPV18 E6 peptides comprising the sequences set forth in SEQ ID NOs: 3930, 3945, and 5237, wherein each HPV18 E6 peptide comprises one of the sequences.
61. The method of claim 44, wherein each tumor-associated antigen is independently from a tumor-associated protein selected from the group consisting of HPV16 E6 oncoprotein, HPV16 E7 oncoprotein, HPV18 E6 oncoprotein, HPV18 E7 oncoprotein, HPV31 E6 oncoprotein, HPV31 E7 oncoprotein, HPV45 E6 oncoprotein, HPV45 E7 oncoprotein, HPV52 E6 oncoprotein, HPV52 E7 oncoprotein, HPV58 E6 oncoprotein, and HPV58 E7 oncoprotein.
62. The method of claim 61, wherein each tumor-associated protein comprises the sequence set forth in any one of SEQ ID NOs: 3652-3663, respectively.
63. The method of claim 61, wherein each tumor-associated antigen is an MHC-I- restricted peptide. 93155272.1 42060734-783069 64. The method of claim 63, wherein each tumor-associated MHC-I-restricted peptide comprises the amino acid sequence set forth in one of SEQ ID NOs: 3664-5103.
65. The method of claim 61, wherein the tumor-associated protein is HPV16 E7 oncoprotein.
66. The method of claim 65, wherein the tumor-associated antigens comprise an MHC-I-restricted peptide comprising the amino acid sequence RAHYNIVTF (SEQ ID NO: 3863) or QAEPDRAHYNIVTFCCKCD (SEQ ID NO: 5104).
67. The method of claim 66, wherein the HPV antigens comprise the MHC-I- restricted HPV16 L1 peptide comprising the amino acid sequence set forth in SEQ ID NO: 1776 and the VZV antigens comprise the truncated VZV gE comprising the amino acid sequence set forth in SEQ ID NO:
2.
68. The method of any one of claims 44-67, wherein the composition comprises or is administered in combination with an adjuvant.
69. The method of claim 68, wherein the adjuvant comprises one or more of poly(I:C), poly-ICLC, a 3-O-desacyl-4’-monophosphoryl lipid A (MPL), QS-21, aluminum hydroxide, and aluminum hydroxyphosphate.
70. The method of claim 69, wherein the adjuvant comprises poly(I:C).
71. The method of claim 69, wherein the adjuvant comprises MPL.
72. The method of claim 71, wherein the adjuvant further comprises QS21.
73. The method of claim 69, wherein the adjuvant comprises AS01B. 93155272.1 43060734-783069 74. The method of claim 73, wherein the composition comprises the truncated VZV gE protein comprising the amino acid sequence set forth in SEQ ID NO:
2.
75. The method of claim 74, wherein the composition is SHINGRIX.
76. The method of claim 75, wherein the adjuvant further comprises aluminum hydroxyphosphate.
77. The method of claim 76, wherein the adjuvant is AS04.
78. The method of claim any one of claims 44-77, wherein the composition is administered 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 times, wherein each administration is performed every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 weeks.
79. The method of claim any one of claims 44-78, wherein the cancer is a solid tumor, and wherein the dose of the one or more antigens is determined relative to tumor volume.
80. The method of claim 79, wherein the dose is at least 1 μg / cm3.
81. The method of claim any one of claims 44-80, wherein the one or more antigens are administered in two or more escalating doses.
82. The method of claim 81, wherein the dose of the one or more antigens is determined individually for the subject.
83. The method of claim 81 or 82, wherein the starting dose of the one or more antigens is determined by an immune assay on autologous peripheral blood mononuclear cells. 93155272.1 44060734-783069 84. The method of claim 81 or 82, wherein the starting dose of the one or more antigens is determined by a delayed-type hypersensitivity skin test.
85. The method of claim of claim 81, wherein each subsequent dose after an immediately preceding dose is escalated until an objective is achieved in the subject, wherein the objective is selected from the group consisting of: an objective clinical response in the subject, shrinkage of the cancer, and a substantial toxicity in the subject.
86. The method of claim 85, wherein after the objective is achieved, a subsequent dose of the antigens or peptides is maintained or decreased relative to a preceding dose; or no additional composition is administered to the subject.
87. A method of treating a cancer in a dog in need thereof, comprising one or more peptides each independently comprising the sequence set forth in one of SEQ ID NOs: 5106- 5234; wherein the dog has been previously immunized against a Rabies virus with a Rabies vaccine; and wherein the composition is administered at the site of the cancer.
88. The method of claim 87, wherein the composition comprises peptides comprising the sequences set forth in SEQ ID NOs: 5106-5234, wherein each peptide comprises one of the sequences.
89. The method of claim 87, wherein the composition comprises is or administered in combination with an adjuvant.
90. The method of claim 89, wherein the adjuvant comprises a Toll-like Receptor 3 (TLR3) agonist. 93155272.1 45060734-783069 91. The method of claim 90, wherein the TLR3 agonist comprises poly(I:C).
92. The method of claim 87, wherein the cancer is a solid tumor.
93. The method of claim 87, wherein the Rabies vaccine comprises one or more of NOBIVAC®, VANGUARD®, and IMRAB®. 93155272.1 46