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OwnerDapeng LI, Andrew James MCMICHAEL +6inventors
InventorsDapeng LI, Andrew James MCMICHAEL, Simon BRACKENRIDGE, Geraldine GILLESPIE, Mihai AZOITEI, Lucy C. WALTERS, Kevin O. Saunders, Barton F. HAYNES
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The present invention provides affinity matured 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 recombinant.lv 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 monoclonal antibodies were subject to one or more rounds of affinity 7 maturation. The invention provides methods for using affinity matured HLA-E-VL9 mAbs to modulate NK and/or CD8+T-cell function as part of immunotherapeutic strategies.
A recombinant HLA-E-VL9 monoclonal antibody, or an antigen binding fragment thereof, which binds to an HLA-E-VL9 complex and comprises a variable heavy (Vh) domain and a variable light (Vl) domain that have amino acid sequences that have an overall 80% sequence identity to the Vh and Vl domains of an antibody listed in Table 1, or wherein the Vh domain and Vl domain each have at least 80% sequence identity to the Vh and Vl domains, respectively, of an antibody listed in Table 1.
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A humanized HLA-E-VL9 monoclonal antibody, or an antigen binding fragment thereof, which specifically binds to an HLA-E-VL9 complex and comprises:
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The antibody, or the antigen binding fragment thereof, according to any of the preceding claims, wherein binding specificity of the antibody or the fragment thereof requires the peptide of the HLA-E-VL9 complex to have an amino acid sequence according to the following motif:
The antibody, or the antigen binding fragment thereof, according to any of the preceding claims, wherein binding specificity of the antibody or the fragment thereof requires the peptide of the HLA-E-VL9 complex to have an amino acid sequence according to the following motif:
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An in vitro transcription system to synthesize ribonucleic acids (RNAs) encoding antibodies of the invention, comprising:
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Dependencies are inferred from the claim text.