METHODS AND COMPOSITIONS FOR TARGETING A COMPLEX COMPRISING NON-CLASSICAL HLA-I AND NEOANTIGEN IN CANCER
Disclosed herein are methods and compositions for targeting a complex comprising a non-classical HLA-I and a neoantigen in cancer. Further disclosed herein are antibodies that selectively bind to a complex comprising a non-classical HLA-I and a neoantigen, as well as methods of use thereof.
1 - 39 . (canceled)
40 . A method of treating cancer in an individual in need thereof, comprising administering to the individual an antibody that selectively binds to a complex comprising a non-classical HLA-I and a neoantigen.
41 . The method of claim 40 , wherein the antibody does not have a binding affinity to (i) the non-classical HLA-I alone; or (ii) the neoantigen alone.
42 - 45 . (canceled)
46 . The method of claim 40 , wherein the neoantigen comprises, consisting essentially of, or consisting of a sequence according to SEQ ID NO: 3 (VMAPRTLFL), SEQ ID NO: 13 (VMAPRTLIL), SEQ ID NO: 14 (VMPPRTLLL), SEQ ID NO: 31 (VMAPRTLVL), SEQ ID NO: 19 (YLLPRRGPRL), SEQ ID NO: 20 (AISPRTLNA), SEQ ID NO: 21 (SQAPLPCVL), SEQ ID NO: 15 (YLLEMLWRL), SEQ ID NO: 16 (YMLDLQPETT), SEQ ID NO: 22 (QMRPVSRVL), SEQ ID NO: 23 (ALALVRMLI), SEQ ID NO: 24 (SQQPYLQLQ), SEQ ID NO: 25 (AMAPIKTHL), SEQ ID NO: 26 (AMAPIKVRL), SEQ ID NO: 17 (YLLPAIVHI), SEQ ID NO: 27 (ILDQKINEV), SEQ ID NO: 28 (GVYDGEEHSV), SEQ ID NO: 29 (KVLEYVIKV), SEQ ID NO: 18 (SLLMWITQV), SEQ ID NO: 30 (YLEPGPVTV), SEQ ID NO: 32 (SLLEKSLGL), SEQ ID NO: 22 (QMRPVSRVL), SEQ ID NO: 33 (WIAAVTIAA), SEQ ID NO: 34 (TSDMPGTTL), SEQ ID NO: 35 (MLALLTQVA), SEQ ID NO: 36 (QMFEGPLAL), SEQ ID NO: 37 (VLWDRTFSL), SEQ ID NO: 38 (TLFFQQNAL), SEQ ID NO: 1 (GLADKVYFL), or SEQ ID NO: 2 (ILSPTVVSI).
47 - 53 . (canceled)
54 . The method of claim 40 , wherein the non-classical HLA-I is HLA-E, HLA-F, HLA-G, or HLA-H.
55 . The method of claim 40 , wherein the non-classical HLA-I is HLA-E.
56 . The method of claim 55 , wherein the HLA-E is HLA-E*0101 or HLA-E*0103.
57 . (canceled)
58 . The method of claim 56 , wherein the antibody selectively binds to the complex comprising:
(a) the HLA-E*0101 and the neoantigen;
(b) the HLA-E*0103 and the neoantigen; or
(c) the HLA-E*0101 and the neoantigen, and the HLA-E*0103 and the neoantigen.
59 . The method of claim 55 , wherein the complex comprises the HLA-E and VMAPRTLFL (SEQ ID NO: 3), HLA-E and VMAPRTLIL (SEQ ID NO: 13), HLA-E and VMPPRTLLL (SEQ ID NO: 14), HLA-E and VMAPRTLVL (SEQ ID NO: 31), HLA-E and YLLPRRGPRL (SEQ ID NO: 19), the HLA-E and AISPRTLNA (SEQ ID NO: 20), the HLA-E and SQAPLPCVL (SEQ ID NO: 21), the HLA-E and YLLEMLWRL (SEQ ID NO: 15), the HLA-E and YMLDLQPETT (SEQ ID NO: 16), the HLA-E and QMRPVSRVL (SEQ ID NO: 22), the HLA-E and ALALVRMLI (SEQ ID NO: 23), the HLA-E and SQQPYLQLQ (SEQ ID NO: 24), the HLA-E and AMAPIKTHL (SEQ ID NO: 25), the HLA-E and AMAPIKVRL (SEQ ID NO: 26), the HLA-E and YLLPAIVHI (SEQ ID NO: 17), the HLA-E and ILDQKINEV (SEQ ID NO: 27), the HLA-E and GVYDGEEHSV (SEQ ID NO: 28), the HLA-E and KVLEYVIKV (SEQ ID NO: 29), the HLA-E and SLLMWITQV (SEQ ID NO: 18), the HLA-E and YLEPGPVTV (SEQ ID NO: 30), the HLA-E and SLLEKSLGL (SEQ ID NO: 32), the HLA-E and QMRPVSRVL (SEQ ID NO: 22), the HLA-E and WIAAVTIAA (SEQ ID NO: 33), the HLA-E and TSDMPGTTL (SEQ ID NO: 34), the HLA-E and MLALLTQVA (SEQ ID NO: 35), the HLA-E and QMFEGPLAL (SEQ ID NO: 36), the HLA-E and VLWDRTFSL (SEQ ID NO: 37), the HLA-E and TLFFQQNAL (SEQ ID NO: 38), the HLA-E and GLADKVYFL (SEQ ID NO: 1), or the HLA-E and ILSPTVVSI (SEQ ID NO: 2).
60 - 66 . (canceled)
67 . The method of claim 40 , wherein the antibody is a murine antibody, a chimeric antibody, a camelid antibody, a humanized antibody, or a human antibody.
68 . The method of claim 40 , wherein the antibody is a TCR-like antibody.
69 . The method of claim 40 , wherein the antibody is a single domain antibody.
70 . The method of claim 69 , wherein the single domain antibody is a camelid single domain antibody.
71 . The method of claim 40 , wherein the antibody is a multispecific antibody.
72 . The method of claim 40 , wherein the antibody is a multifunctional antibody.
73 . The method of claim 40 , wherein the antibody further comprises a conjugated therapeutic moiety.
74 . The method of claim 40 , wherein the selective binding of the antibody to the complex comprising the non-classical HLA-I and the neoantigen induces an immune response.
75 . The method of claim 74 , wherein the immune response comprises activation of T cells.
76 - 82 . (canceled)
83 . The method of claim 40 , wherein the cancer is breast cancer, kidney cancer, lung cancer, ovarian cancer, colorectal cancer, or a B-cell malignancy.
84 - 173 . (canceled)
174 . The method of claim 40 , wherein the antibody selectively binds to both the non-classical HLA-I and the neoantigen in the complex comprising the non-classical HLA-I and the neoantigen.