Methods of treating cancer with Anti-mica / b antibodies
Patent Information
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- CULLINAN MICA CORP
- Filing Date
- 2026-04-15
- Publication Date
- 2026-07-10
Smart Images
Figure 00000138_0000 
Figure 00000138_0001 
Figure 00000139_0000
Abstract
Description
Methods for Treating Cancer with Anti-MICA / B Antibodies This paper provides methods for treating cancer with antibodies or antigen-binding fragments thereof that specifically bind to MICA / B, said antibodies or antigen-binding fragments having the heavy chain, light chain, variable heavy chain domain (VH), variable light chain domain (VL), and complementarity-determining region (CDR) disclosed herein. Abstract
Claims
CLAIMSWhat is claimed is:
1. A method of treating endometrial cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of an antibody that binds to MICA / B (an anti-MICA / B antibody).
2. The method of claim 1, wherein the subject has previously been treated with a PD-1 inhibitor (e.g., an anti-PD-1 antibody).
3. The method of claim 1, wherein the subject has previously been treated with a VEGF inhibitor or hormonal therapy.
4. The method of claim 1, wherein the subject has not previously been treated with a PD-1 inhibitor (e.g., an anti-PD-1 antibody).
5. The method of any of claims 1-4, wherein the endometrial cancer is HER2+.
6. The method of any of claims 1-4, wherein the endometrial cancer is one or both of ER+ or PR+.
7. A method of treating parotid cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of an antibody that binds to MICA / B (an anti- MICA / B antibody).
8. The method of claim 7, wherein the parotid cancer overexpresses one or both of EGFR and HER2.
9. The method of claim 7 or 8, wherein the parotid cancer is a mucoepidermoid parotid cancer.
10. The method of any of the preceding claims, wherein the cancer is mutant for one or more of: EGFR, TP53, HER2, PTEN, ARID1A, CTNNB1, or PLK3R1.
11. A method of treating cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of an antibody that binds to MICA / B (an anti- M1CA / B antibody), wherein the subject has previously been treated with:(i) a VEGF inhibitor;(ii) an EGFR inhibitor; and / or(iii) a hormone therapy.
12. The method of claim 11, wherein the subject responded (e.g., had a complete response or partial response) to the VEGF inhibitor, the EGFR inhibitor or the hormone therapy, wherein optionally the subject had a period of response of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, 36, 42, 48, 54, 60 months or more.
13. The method of claim 12, wherein the subject progressed following a period of response to the VEGF inhibitor, the EGFR inhibitor, or the hormone therapy.
14. The method of claim 13, wherein the administration of the anti-MICA / B antibody is after the progression following the period of response to the VEGF inhibitor, the EGFR inhibitor, or the hormone therapy.
15. The method of claim 11, wherein the subject had stable disease upon administration of the VEGF inhibitor, the EGFR inhibitor or the hormone therapy, wherein optionally the subject had a period of stable disease of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, 36, 42, 48, 54, 60 months or more.
16. The method of claim 11, wherein treatment with the VEGF inhibitor, the EGFR inhibitor, or the hormone therapy ceased before initiation of administration of the anti-MICA / B antibody.
17. The method of claim 11, wherein treatment with the VEGF inhibitor, the EGFR inhibitor, or the hormone therapy continues after initiation of administration of the anti- MICA / B antibody.
18. The method of claim 11, wherein the subject progressed upon treatment with the VEGF inhibitor, the EGFR inhibitor, or the hormone therapy.
19. The method of any one of the preceding claims, where after administration of the anti- MICA / B antibody, the subject has a response (e.g., a complete response or partial response) or stable disease.
20. The method of claim 19, wherein the response after administration of the anti-MICA / B antibody is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, 36, 42, 48, 54, 60 months or more.
21. The method of any one of claims 11-20, wherein the EGFR inhibitor comprises a small molecule tyrosine kinase inhibitor (TKI) (e.g., gefitinib, erlotinib, afatinib, dacomitinib, or osimertinib) or an anti-EGFR antibody, e.g., cetuximab, panitumumab, or necitumumab).
22. The method of 11-20, wherein the VEGF inhibitor comprises a small molecule tyrosine kinase inhibitor (TKI) (e.g., sunitinib, sorafenib, axitinib, pazopanib, or lenvatinib), or an anti- VEGF antibody (e.g., bevacizumab or ranibizumab).
23. The method of 11-20, wherein the hormone therapy comprises an aromatase inhibitor (Al) (e.g., anastrozole), a selective estrogen receptor modulator (SERM), a leuteinizinghormone-releasing hormone (LHRH) agonist, an anti-androgen, a CYP17 inhibitor, a progestin, an adrenolytic, or an estrogen receptor antagonist.
24. A method of treating cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of an antibody that binds to MICA / B (an anti- MICA / B antibody), wherein the subject has previously been treated with a PD-1 inhibitor (e.g., an anti-PD-1 antibody), wherein:(i) the subject responded (e.g., had a complete response or partial response) to the PD-1 inhibitor; or(ii) the subject had stable disease upon administration of the PD-1 inhibitor.
25. The method of claim 24, wherein, the subject had a period of response of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, 36, 42, 48, 54, 60 months or more.
26. The method of claim 25, wherein the subject progressed following a period of response to the PD-1 inhibitor.
27. The method of claim 26, wherein the administration of the anti-MICA / B antibody is after the progression following the period of response to the PD- 1 inhibitor.
28. The method of claim 24, wherein, wherein the subject had a period of stable disease of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, 36, 42, 48, 54, 60 months or more.
29. The method of claim 24, wherein treatment with the PD-1 inhibitor ceased before initiation of administration of the anti-MICA / B antibody.
30. The method of claim 24, wherein treatment with the PD-1 inhibitor continues after initiation of administration of the anti-MICA / B antibody.
31. The method of any of the preceding claims, where after administration of the anti- MICA / B antibody, the subject has a response (e.g., a complete response or partial response) or stable disease.
32. The method of claim 37, wherein the response after administration of the anti-MICA / B antibody is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, 36, 42, 48, 54, 60 months or more.
33. The method of any one of the preceding claims, wherein the PD-1 inhibitor is an anti- PD-1 antibody.
34. The method of any one of the preceding claims, wherein the anti-PD-1 inhibitor comprises pimivalimab, pembrolizumab, nivolumab, cemiplimab, AMP-224, APM-514, or spartali zumab.
35. The method of any one of the preceding claims, wherein the subject has previously been treated with a VEGF inhibitor, an EGFR inhibitor, and / or a hormone therapy.
36. A method of treating cancer in a subject, the method comprising:(i) administering to the subject first dose of an antibody that binds to MICA / B (an anti-MICA / B antibody), and(ii) administering to the subject a therapeutically effective amount of a corticosteroid prior to the first dose of the anti-MICA / B antibody.
37. The method of claim 36, wherein the corticosteroid is administered 30 - 60 minutes prior to administration of the anti-MICA / B antibody.
38. The method of claim 36 or 37, wherein the corticosteroid is administered at a dose of between about 2 mg to about 50 mg.
39. The method of claim 36 or 37, wherein the corticosteroid is administered at a dose of about 10 mg.
40. The method of any one of claims 36-39, wherein the corticosteroid is administered orally or intravenously.
41. The method of any one of claims 36-40, wherein the method further comprises administering one or more subsequent doses of the anti-MICA / B antibody.
42. The method of claim 41, wherein the corticosteroid is administered prior to the first dose of the anti-MICA / B antibody but is not administered prior to the one or more subsequent doses of the anti-MICA / B antibody.
43. The method of any of claims 36-42, wherein the corticosteroid is dexamethasone.
44. The method of claim 44, wherein the cancer is a tumor of the female genital tract, a salivary gland tumor, a breast cancer, a prostate cancer, a lung cancer, or a colon cancer.
45. The method of claim 44, wherein: the tumor of the female genital tract comprises an endometrial tumor, an ovarian cancer, or a cervical cancer; the salivary gland tumor comprises a mucoepidermoid tumor such as a parotid tumor.
46. The method of any one of the preceding claims, wherein the subject has a cancer that is a parotid gland cancer, a cervical cancer, an endometrial cancer, a breast cancer, a colon cancer, an ovarian cancer, a prostate cancer, a sarcoma, a melanoma, an adenoid cystic salivary tumor, a peritoneal mesothelioma, a squamous cell carcinoma of the rectum, a leiomyosarcoma, acolorectal cancer, a kidney cancer, a thyroid cancer, an NSCLC, a duodenum cancer, a pancreatic cancer, a mediatinal intimal sarcoma, a head and neck cancer, or a caecal cancer.
47. The method of any of the preceding claims wherein the subject has a cancer characterized by one or more of the following: a cancer characterized by a low level of PD-L1 expression; a cancer characterized by a high level of PD-L1 expression; a cancer characterized by a low tumor mutation burden (TMB); a cancer characterized by a high tumor mutation burden (TMB); an immunologically cold cancer; an immunologically hot cancer; a hormone- sensitive cancer; a cancer characterized by an overexpression of oncogenic drivers; or a cancer that expresses one or more of: EGFR, ER, PR, or HER2.
48. The method of any of the preceding claims wherein the subject has a cancer that has metastasized.
49. The method of any one of the preceding claims, wherein the subject has previously received a therapy comprising a chemotherapy.
50. The method of any one of the preceding claims, wherein the anti-MICA / B antibody is administered at a dose of about 3 mg / kg to about 10 mg / kg.
51. The method of any one of the preceding claims, wherein the anti-MICA / B antibody is administered to the subject according to a dosing interval (e.g., a cycle).
52. The method of any one of the preceding claims, wherein the dosing interval comprises a three-week cycle, and wherein the anti-MICA / B antibody is administered once every three weeks (Q3W).
53. The method of claim 51 or 52, wherein the dosing interval is repeated at least 1 time, at least 2 times, at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 7 times, at least 8 times, at least 9 times, or at least 10 times.
54. The method of claim 53, wherein the repeated dosing interval is performed over at least 2 weeks, 3 weeks, 4 weeks, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 3 years, 4 years, or 5 years.
55. The method of any one of the preceding claims, wherein the anti-MICA / B antibody comprises a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) of SEQ ID NO: 1, a light chain complementarity determining region (LCDR2) of SEQ ID NO: 2, a light chain complementarity determining region 3 (LCDR3) of SEQ ID NO: 3 and a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) of SEQ ID NO: 4, a heavy chain complementarity determining region 2 (HCDR2) of SEQ ID NO: 5, and a heavy chain complementarity determining region 3 (HCDR3) of SEQ ID NO: 6.
56. The method of claim 55, wherein the VL comprises the amino acid sequence of SEQ ID NO: 7, or an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto.
57. The method of claim 55 or 56, wherein the VH comprises the amino acid sequence of SEQ ID NO: 8, or an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto.
58. The method of any one of claims 55-57, wherein the light chain comprises the amino acid sequence of SEQ ID NO: 9, or an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto.
59. The method of any one of claims 55-58, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 10, or an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto.
60. The method of any one of the preceding claims, wherein the anti-MICA / B antibody specifically binds to a MICA protein, a MICB protein, or both MICA and MICB protein.
61. The method of any one of the preceding claims, wherein the anti-MICA / B antibody binds to an alpha-3 domain of a MICA protein, a MICB protein, or both MICA and MICB protein.
62. The method of claim 60 or 61, wherein the MICA protein is membrane-bound MICA protein, soluble MICA protein, or both.
63. The method of claim 60 or 61 , wherein the MICB protein is membrane-bound MICB protein, soluble MICB protein, or both.
64. The method any one of the preceding claims, wherein the anti-MICA / B antibody is selected from a whole immunoglobulin, an scFv, a Fab, a F(ab’)2, or a disulfide linked Fv.
65. The method of any one of the preceding claims, wherein the anti-MICA / B antibody is an IgG or IgM.
66. The method of any one of the preceding claims, wherein the anti-MICA / B antibody is a humanized or a chimeric antibody.
67. The method of any one of the preceding claims, wherein the method further comprises administering to the subject an effective amount of a PD- 1 inhibitor.
68. The method of claim 67, wherein the PD-1 inhibitor is an anti-PD-1 antibody.
69. The method of claim 67 or 68, wherein the anti-PD-1 inhibitor comprises pimivalimab, pembrolizumab, nivolumab, cemiplimab, AMP-224, APM-514, or spartalizumab.
70. A method of treating multiple myeloma in a subject, the method comprising administering to the subject a therapeutically effective amount of an antibody that binds to MICA / B (an anti-MICA / B antibody).
71. The method of claim 70, further comprising administering to said subject a therapeutically effective amount of an immunomodulatory drug.
72. The method of claim 71, further comprising administering to said subject a therapeutically effective amount of dexamethasone.
73. The method of any of claims 70 to 72, wherein after administration of the anti-MICA / B antibody, the subject has a response (e.g., a complete response or partial response) or stable disease.
74. The method of any of claims 70 to 73, wherein said subject has relapsed / refractory multiple myeloma.
75. The method of any of claims 70 to 74, wherein said subject is non-responsive to corticosteroids, melphalan, or a combination of vincristine, doxorubicin, dexamethasone.
76. The method of claim 70, further comprising administering to the subject a therapeutically effective amount of a corticosteroid prior to the first dose of the anti-MICA / B antibody.
77. The method of claim 76, wherein the corticosteroid is administered 30 - 60 minutes prior to administration of the anti-MICA / B antibody.
78. The method of claim 76, wherein the corticosteroid is administered at a dose of between about 2 mg to about 50 mg.
79. The method of claim 76 to 78, wherein the corticosteroid is administered at a dose of about 10 mg.
80. The method of any one of claims 76 to 79, wherein the corticosteroid is administered orally or intravenously.
81. The method of any one of claims 76-80, wherein the method further comprises administering one or more subsequent doses of the anti-MICA / B antibody.
82. The method of claim 81 , wherein the corticosteroid is administered prior to the first dose of the anti-MICA / B antibody but is not administered prior to the one or more subsequent doses of the anti-MICA / B antibody.
83. The method of any of claims 76-82, wherein the corticosteroid is dexamethasone.