Antibodies that target hla-e-host peptide complexes and uses thereof

Patent metadata

Field	Value
Publication number	US-2025051454-A1
Application number	US-202118245540-A
Country	US
Kind code	A1
Filing date	Sep 15, 2021
Priority date	Sep 15, 2020
Publication date	Feb 13, 2025
Grant date	—

Abstract

Recombinant monoclonal antibodies (mAbs) and fragments that bind specifically to an HLA-E-peptide complex, including HLA-E-VL9 complexes, and regulate the cytotoxicity effector cell function of NK and/or CD8+ T-cells positive for cell-surface expression of NKG2A (“NKG2A+”). Herein, monoclonal antibodies were recombinantly derived from isolated functional HLA-E-VL9-specific mAbs from HLA-E-VL9 peptide-immunized HLA-B transgenic mice and from the naive human B cell repertoire. Such antibodies are capable of regulating effector cell cytotoxicity and can preferentially recognize HLA-E-VL9 peptide complexes expressed on the surface of tumor cells. The invention provides methods for using HLA-E-VL9 m Abs to modulate NK and/or CD8+ T-cell function as part of immunotherapeutic strategies.

First claim

1 - 60 . (canceled)

61 . A recombinant antibody or fragment thereof selected from the group consisting of:
3H4, CA147, 13F11, 10C10, 2D6, CA118, CA119, CA120, CA122, CA123, CA124, CA125, CA127, CA128, CA129, CA130, CA131, CA132, CA133, CA134, CA135, CA136, CA137, CA138, CA139, CA140, CA141, CA143, CA144, CA145, CA146, CA401, 3H4 Gv2, 3H4 Gv3, 3H4 Gv4, 3H4 Gv5, 3H4 Gv6, 3H4 Gv7, 3H4 Gv8, 3H4 Gv9, 3H4 Gv10, 3H4 Gv11, 3H4 Gv12, CA147hexa, CA147sortaNP, 3H4hexa, and 3H4sortaNP; wherein 3H4 comprises a heavy chain variable region (VH) comprising an amino acid sequence at least 80% identical to SEQ ID NO: 128 and a light chain variable region (VL) comprising an amino acid sequence at least 80% identical to SEQ ID NO: 129; wherein CA147 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 184 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 185; wherein 13F11 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 130 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 131; wherein 10C10 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 132 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 133; wherein 2D6 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 134 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 135; wherein CA118 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 136 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 137; wherein CA119 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 138 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 139; wherein CA120 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 140 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 141; wherein CA122 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 142 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 143; wherein CA123 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 144 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 145; wherein CA124 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 146 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 147; wherein CA125 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 148 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 149; wherein CA127 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 150 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 151; wherein CA128 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 152 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 153; wherein CA129 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 154 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 155; wherein CA130 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 156 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 157; wherein CA131 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 158 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 159; wherein CA132 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 156 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 141; wherein CA133 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 160 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 161; wherein CA134 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 162 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 163; wherein CA135 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 164 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 157; wherein CA136 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 165 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 166; wherein CA137 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 167 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 157; wherein CA138 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 168 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 169; wherein CA139 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 170 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 171; wherein CA140 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 172 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 173; wherein CA141 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 174 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 175; wherein CA143 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 176 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 177; wherein CA144 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 178 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 179; wherein CA145 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 180 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 181; wherein CA146 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 182 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 183; wherein CA401 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 186 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 187; wherein 3H4 Gv2 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 35 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 129; wherein 3H4 Gv3 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 36 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 129; wherein 3H4 Gv4 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 37 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 129; wherein 3H4 Gv5 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 38 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 129; wherein 3H4 Gv6 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 39 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 129; wherein 3H4 Gv7 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 40 and a VL comprising an amino acid sequence at least 80% identical to SEQ ID NO: 129; wherein 3H4 Gv8 comprises a VH comprising an amino acid sequence at least 80% identical to SEQ ID NO: 41 and a VL comprising an amino acid sequence at least 80% identical to SE

Assignees

• Univ Duke
• The Chancellor Masters And Scholars Of The Univ Of Oxford

Inventors

• Haynes Barton F
• Saunders Kevin O
• Li Dapeng
• Azoitei Mihai
• Walters Lucy C
• Gillespie Geraldine
• Brackenridge Simon
• Mcmichael Andrew James

Classifications

• C07K16/104

  Severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2] · CPC title

• C07K2317/32

  specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/35

  Valency · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title